Impaired intratumoral dendritic cell function and potential predictive value of dendritic cells markers for metastasis in malignant salivary gland tumors

Background: The differentiation between primary and metastatic salivary gland neoplasms (SGNs) helps in determining appropriate management strategies, including the need for additional diagnostic tests, surveillance, or aggressive treatment. The purpose of this study was to identify and quantify the immature and mature dendritic cells (DCs) in metastatic and no metastatic SGNs and determine its association with clinicopathological findings. Material and Methods: Cross-sectional, observational, and descriptive study that includes 33 malignant salivary gland neoplasms [MSGN (6, 18.1% metastatic)], and 22 pleomorphic adenomas (PA), as a control group. Clinical and histopathological characteristics were obtained. Immunohistochemistry for human leukocyte antigen Drelated (HLA-DR), CD1a, CD83, and Ki-67 proteins was done. Positive intra- and peritumoral DCs were counted. Results: Individuals with MSGN had a lower density of intratumoral HLA-DR+ cells than those with PA (p=0.001), Ki-67 immunostaining was significantly higher in MSGN than in PA (6% vs. 1.4%, p<0.001). Metastatic MSGN showed less intratumoral CD1a+ than non-metastatic (3.2 vs. 165.1, p=0.001). No differences in intra- and peritumoral CD83+ cells were found between benign and malignant SGN. Conclusions: These results suggest that the immune-protective function of intratumoral DCs is compromised in MSGNs. DCs markers may represent useful prediction tools for metastases in salivary gland malignancies, with crucial implications in the implementation of appropriate disease management strategies. (AU)

Oral HPV-associated dysplasia: is koilocytic dysplasia a separate entity?

Oral epithelial dysplasia associated with high-risk HPV infection has received different names since its initial description, such as oral Bowenoid lesions, HPV-associated intraepithelial neoplasia, and oral koilocytic dysplasia. Some features, identified in more or less quantity in some of the descriptions, like apoptotic keratinocytes, karyorrhexis, and mitosoid figures, are intricately connected to viral transcriptional status and, consequently, viral load. Since the variety in terminology has introduced diagnostic confusion within medical and research communities, establishing a uniform and standardized approach to diagnosing HPV-oral epithelial dysplasia is crucial for accurate and early diagnoses and holds significant implications for patient outcomes, particularly in high-risk individuals.

Clinicopathological and molecular approaches to the diagnosis of oral lesions in Mpox: Case report.

Mpox virus infection (MPXV) has recently been recognized as a public health emergency by the World Health Organization. While several studies have described the clinical characteristics of MPXV-oral lesions, there remains a dearth of information regarding the histological and ultrastructural oral findings. A 24-year-old HIV-positive man presented with a shallow ulcer, covered by a fibrinoid membrane, and surrounded by an erythematous halo in the hard and soft palate. The clinical appearance of the lesion raised suspicion of a viral infection; thus, the diagnosis was based on histological and electronic microscopy findings and confirmed by RT-PCR testing in the skin specimen. This case report aims to offer comprehensive insights into the clinical, histopathological, and ultrastructural features of oral lesions caused by MPXV in an individual with HIV. This report provides valuable information about the characteristics of MPXV infection in the oral mucosa, particularly in people living with HIV.

Oral cancer and precancer in Oral Pathology and Medicine curricula of Mexican dental schools.

OBJECTIVE: To identify the teaching-learning process characteristics of Oral Pathology and Medicine (OP&M) related to oral potentially malignant disorders (OPMDs) and oral cancer (OC), in the dental schools' curricula in Mexico, to analyze the approach given to this topic worldwide, and to provide the possible solution strategies. MATERIALS AND METHODS: Questionnaires were sent to OP&M deans and professors from public Mexican Universities to explore the curriculum and academic profile of the dental schools. The recommendations gathered from a workshop with expert professors on the challenges in OPMD/OC teaching were reported. RESULTS: Twenty-two dental schools participated (22 deans, 30 professors). The most widely used strategies were clinical-case resolving (86%) and presentations (73%). Although 77.3% of the programs included maxillofacial lesions, only 40.9% contemplated OPMD/OC. Only 45% of the programs developed community activities for early OC detection. The workshop recommendations were (i) multidisciplinary approach to OPMD/OC teaching, involving OP&M professors in other dental and nondental courses; (ii) implementation of the most effective teaching techniques (currently, problem-based learning and clinical-case presentation) in OP&M curricula; (iii) education of OP&M professors on teaching-learning processes. CONCLUSIONS: These recommendations from the Mexican context, integrated with similar experiences from other countries could contribute to develop a unique, internationally acknowledged OP&M curriculum.

Exposing the Great Imitator: Proposal for a Holistic Diagnosis of Oral Secondary Syphilis in People Living with HIV.

Oral secondary syphilis may mimic various infectious, neoplastic, or immune-mediated processes; hence, its diagnosis may represent a challenge. Early diagnosis of syphilis, a disease that has increased in recent decades, is essential for adequate management, particularly in people living with HIV (PLWH). This study aimed to comprehensively characterize oral secondary syphilis in a group of 47 PLWH. A group of PLWH with oral secondary syphilis attending four HIV-referral centers in Mexico City was included (2004-2021). Clinical and laboratory data were retrieved, and an exhaustive oral examination was performed following the established criteria. Demographic, clinicopathological, immunohistochemical, and serological features of the patients were analyzed. Approximately 11% of PLWH with oral secondary syphilis demonstrated negative Venereal Disease Research Laboratory tests. A noticeable feature was the absence of symptoms in 95.7% of cases, despite the clinically evident appearance of the lesions. In contrast to previous results, 18% of ulcerations were detected to be deep, crateriform, and infiltrative, and 22% of the mucous patches were highly keratotic lesions. Most samples (77.3%) showed superficial lymphoplasmacytic infiltrates in the superficial lamina propria, with perivascular and perineural patterns, and immunohistochemistry was positive in 66.7% of the cases. The "great imitator" appears not only clinically but also histopathologically and immunohistochemically, where features may be comparable with those of chronic inflammatory processes, deep infections, or malignant processes. Although not recommended as a routine assay, IHC could be a critical tool, particularly in PLWH with atypical clinical features or with negative and/or dubious serology.

Viruses and oral diseases in HIV-infected individuals on long-term antiretroviral therapy: What are the risks and what are the mechanisms?

As a result of the extension of life span produced by increasing access to combined antiretroviral therapy, people living with HIV/AIDS (PLWH) face new challenges from comorbidities. Although advances in medical care for HIV infection have dramatically reduced opportunistic infections and AIDS-defining cancers, some non-AIDS-defining cancers (NADC) and specific oral diseases such as periodontitis and salivary gland disease are now more prevalent. Cancer prevention is, therefore, a priority issue in care of PLWH, stressing both restoration of immune function and reduction of non-HIV cancer risk factors (tobacco in all its forms; areca nut; heavy alcohol consumption; diets lacking antioxidant vitamins and minerals; and oncogenic virus infections) through specific interventions, especially tobacco and areca nut cessation and alcohol moderation. Detection of oral high-risk human papillomaviruses (HR-HPV) and the universal preventive HPV vaccination among PLWH should be promoted to reduce the malignancy burden, along with routine oral examinations which remain the cheapest, most reliable, most reproducible, and non-invasive tool to identify suspicious lesions. Also, considerations of oral inflammation and periodontal health are important to replication and gene expression of viruses in the mouth. Considering that a key risk factor for this scenario is the presence of oncogenic virus infection such as several members of the human herpesvirus and human papillomavirus families, here we analyze the variables involved in the seeming increase in comorbidities in PLWH.

Clinical manifestations and risk factors for oral immune reconstitution inflammatory syndrome in Mexico.

The immune reconstitution inflammatory syndrome (IRIS) is a rare acute complication presenting in people living with HIV (PLWH) within the first 6 months of starting combined antiretroviral therapy (cART). While there is relevant information about its pathogenesis and clinical spectrum, IRIS-oral lesions (IRIS-OLs) have been scarcely described. Thus, to establish the incidence and clinical characteristics of IRIS-OLs, data from a cohort of 158 HIV individuals starting cART, followed for 6 months, were obtained retrospectively. IRIS-OLs developed in 11.4% of the individuals, in a median time of 87.5 days, with oral candidiasis being the most frequent manifestation detected in eight individuals (5.1%). The study emphasizes the importance of the correct diagnosis and management of these lesions.

The challenging diagnosis of overlapping oral primary/secondary syphilis with nonreactive serology.

The prevalence of oral syphilis, known as "the great imitator" because of its diagnostic complexity and varied clinical manifestations, is increasing worldwide, particularly in people living with HIV (PLWH), who could present false-negative serological results. Although some studies have described the variable presentation of oral syphilis in the context of HIV infection, the difficulty in distinguishing between the primary and secondary stages, clinically and histopathologically, underscores the need to describe atypical cases. We report the case of a 28-year-old HIV-positive man presenting with a 3-month history of painless white/red ulcerated lesion on the soft palate. Physical examination revealed an ulcerated lesion with local signs of inflammation. Initial biopsy revealed a nonspecific inflammatory process and immunohistochemistry (IHC) using anti-Treponema pallidum antibodies showed negative results. The results of serological tests for syphilis (Venereal Disease Research Laboratory and fluorescent treponemal antibody-absorption test) were negative on repeated occasions. Nonetheless, polymerase chain reaction (PCR) assay and subsequent IHC for T. pallidum showed positive results, confirming the diagnosis of oral syphilis. This case illustrates that the diagnosis of oral syphilis is challenging in the absence of serological evidence, and specific tests such as PCR and IHC are useful complementary diagnostic tools.

Impact of early recognition of potentially malignant oral disorders on the prognosis in people living with HIV.

Despite the success of combination antiretroviral therapies, people living with HIV (PLWH) are at an increased risk of developing diverse malignancies, including oral cancer. We here present two cases of PLWH where the early diagnosis of potentially malignant disorders in the oral cavity impacted their treatment and survival, remaining free of disease after their complete elimination. These cases demonstrate the importance of oral examinations and tissue biopsies as a part of the close monitoring of PLWH.

CD117 immunoexpression in oral and sinonasal mucosal melanoma does not correlate with somatic driver mutations in the MAPK pathway.

BACKGROUND: Mutations on KIT and downstream genes of MAPK pathway that overstimulate cellular proliferation have been associated with primary oral and sinonasal melanomas (POSNM), but there is limited information that allows the use of personalized therapy. Thus, the aim of the present study was to determine a possible association between the C-KIT immunohistochemical expression with the presence of somatic driver mutations in NRAS, BRAF, KIT, MITF and PTEN on POSNM. METHODS: A retrospective study included 62 tumour samples of an oncological reference centre in Mexico City (17-year period). Immunohistochemistry stain of C-KIT was carried out. Genomic DNA was obtained and used to assess hotspot mutations of KIT, NRAS, BRAF, MITF and PTEN through qPCR. Chi-square, Fisher's exact and the Mann-Whitney U tests were applied when necessary. The significance was set at P < 0.05. RESULTS: Sixty-two cases were included, 74% were positive for C-KIT immunoexpression, all exhibited moderate/strong intensity. Ten (16.1%) samples harboured at least one mutation, 6.4% and 6.6% for NRASQ 61R and BRAFV 600E , respectively, followed by KITK624E (3.2%). No KITL 576P , MITF or PTEN mutations were identified. No significant correlation was observed between mutations and immunostaining (rs = -0.057, P = 0.765). CONCLUSIONS: Regardless of the high immunoexpression of C-KIT, there was no association with the MAPK mutations among POSNM samples. Thus, C-KIT immunohistochemistry is not a reliable tool to detect POSNM candidates for biological therapy.

Type-specific persistence and clearance rates of HPV genotypes in the oral and oropharyngeal mucosa in an HIV/AIDS cohort.

BACKGROUND: Oral high-risk human papillomavirus (HR-HPV) infections are frequent and persistent among the HIV-positive population and are associated with an increased risk for head and neck cancer (HNC). In this study, we sought to determine the incidence, persistence and clearance of HPV infections in oral and oropharyngeal samples from HIV/AIDS subjects. METHODS: A longitudinal, observational and analytical study was performed with an ongoing cohort of HIV/AIDS subjects in Mexico City (September 2013-February 2015). The study was approved by institutional committees, and demographic and clinical data were registered. At the baseline and three-month visits, oral examinations and cytobrush samples were obtained. DNA was purified, quantified and used to detect an HPV-L1 gene fragment by nested PCR, using MY09/MY11 and GP5 + /GP6 + primers. HPV DNA products were purified, sequenced and typed according to HPV databases. Risk factors were assessed, and a multivariate modelling approach was used to determine independent effects. RESULTS: This study included 97 HIV/AIDS individuals (91% men [86.4% of which are men who have sex with men], median age: 36 years, 72.2% under HAART). From the baseline visit, HPV was observed in 55.7% (HR-HPV: 26.8%; HPV-18: 24.1%), with a higher HPV-positive samples for smokers (61.1 vs 32.6%, P = .005). The three-month overall HPV incidence was 33.9%; type-specific HPV persistence was 33.3% (HR-HPV: 13.3%); and 13 of the 33 (39.4%) baseline HPV-positive individuals cleared the infection (HR-HPV: 53.8%). CONCLUSIONS: Although HR-HPV persistence was low, and clearance of the infection was observed in most cases, a close follow-up is necessary, given the increase in HNC among HIV-subjects, particularly HPV-related cancer.

Oral primary localized amyloidosis in HIV-infected patients: the oral face of a described skin lesion.

Oral primary localized amyloidosis should be considered in the diagnosis of oral white lesions such as hyperplastic candidosis, lichen planus and lichenoid reactions; it is not associated with antiretroviral therapy use, systemic involvement or malignant transformation.

Expression of PROX-1 in oral Kaposi's sarcoma spindle cells.

BACKGROUND: The histogenesis of neoplastic spindle cells of Kaposi's sarcoma is still uncertain, but some studies consider it a lymphatic vessel differentiation. Prox-1 is a nuclear transcription factor that plays a major role during embryonic lymphangiogenesis, and it has been considered a specific and sensitive lymphatic endothelial cell marker. The aim of this study was to determine the expression of Prox-1 in oral Kaposi's sarcoma comparing the results with oral benign vascular tumors including capillary hemangiomas and pyogenic granulomas. METHODS: Expression of Prox-1 and HHV-8 was evaluated by immunohistochemistry in 30 oral Kaposi's sarcoma, 5 oral capillary hemangiomas, and 10 oral pyogenic granulomas. The labeling index was expressed as the percentage of positive cells for each case studied. Statistical comparison was performed using the Wilcoxon-Mann-Whitney rank sum test. RESULTS: Twenty-eight (93.3%) and 30 oral Kaposi's sarcoma cases were positive for Prox-1 and HHV-8, respectively, while all oral benign vascular tumors were negative for these markers. The number of Prox-1 and HHV-8 oral Kaposi's sarcoma-positive cells increased significantly from patch/plaque to nodular histological stages. CONCLUSION: The expression of Prox-1 in the neoplastic spindle cells supports the view of a lymphatic differentiation in oral Kaposi's sarcoma. Prox-1 may also be involved in the pathogenesis of oral Kaposi's sarcoma as the number of positive spindle cells increased progressively from patch to nodular stages and could be eventually useful as an additional diagnostic tool for differential diagnosis between oral Kaposi's sarcoma and benign oral vascular lesions.

HPV oral lesions in HIV-infected patients: the impact of long-term HAART.

BACKGROUND: Since the introduction of highly active antiretroviral therapy (HAART), an increase in the frequency of human papillomavirus-associated oral lesions (HPV-OL) has been observed. Thus, the aim of this study was to determine the prevalence and factors associated with HPV-OL in Mexican HIV-infected patients, as well as its genotyping, in the HAART era. METHODS: In a cross-sectional study developed at an HIV/AIDS referral center in Mexico City, HIV-infected patients were consecutively included from 2004 to 2011. An oral exam was performed; lymphocyte CD4(+) count, HIV-viral load, CDC-stage, and HAART use were recorded. HPV-OL samples were taken for routine histopathological analysis (H-E) and HPV-DNA amplification/sequencing. Logistic regression models were performed and the interactions tested using the STATA software. RESULTS: Among 787 HIV patients, 55 (6.9%) showed HPV-OL. HPV-OLs were independently associated with age (≥40 years) and with a longer time of HAART use (≥12 months). The most frequent lesion was squamous cell papilloma in 22 (40%) cases, followed by multifocal epithelial hyperplasia in 15 (27.3%) cases. Labial mucosa was the most common site involved (56.4%). Of the sequences obtained, 65.4% corresponded to low risk and 11.5% to high risk. Mixed high- and low-risk infection were identified in 7.7% of the cases. CONCLUSIONS: Human papillomavirus-associated oral lesions were associated with older age and longer HAART use. All lesions were benign in nature and most of the HPV sequences corresponded to low-risk types. The rise of HPV-OLs in HIV patients on HAART may be related with the longer life expectancy of individuals with an impaired immune system rather than a direct effect of HAART.

Clinical Spectrum of Oral Secondary Syphilis in HIV-Infected Patients.

Background. Oral lesions may constitute the first clinical manifestation in secondary syphilis, but detailed descriptions in HIV-infected individuals are scarce. Objective. To describe the clinical characteristics of oral secondary syphilis in HIV-infected patients and its relevance in the early diagnosis of syphilis. Methods. Twenty HIV/AIDS adult subjects with oral secondary syphilis lesions presenting at two HIV/AIDS referral centers in Mexico City (2003-2011) are described. An oral examination was performed by specialists in oral pathology and medicine; when possible, a punch biopsy was done, and Warthin-Starry stain and immunohistochemistry were completed. Intraoral herpes virus infection and erythematous candidosis were ruled out by cytological analysis. Diagnosis of oral syphilis was confirmed with positive nontreponemal test (VDRL), and, if possible, fluorescent treponemal antibody test. Results. Twenty male patients (median age 31.5, 21-59 years) with oral secondary syphilis lesions were included. Oral lesions were the first clinical sign of syphilis in 16 (80%) cases. Mucous patch was the most common oral manifestation (17, 85.5%), followed by shallow ulcers (2, 10%) and macular lesions (1, 5%). Conclusions. Due to the recent rise in HIV-syphilis coinfection, dental and medical practitioners should consider secondary syphilis in the differential diagnosis of oral lesions, particularly in HIV-infected patients.

Kaposi's sarcoma of the head and neck: a review.

Important advances in Kaposi's sarcoma (KS) knowledge have been achieved, but KS is still a dilemma. It is an angioproliferative disorder classified as an intermediate neoplasm due to the absence of conventional clinical features of malignancy, but at the moment, it remains unclear if KS could be considered a reactive proliferation of endothelial cells and spindle cells, a true malignancy or both. In this review, the authors address the main epidemiological, clinical, and biological features, of the five types of KS, with emphasis on KS affecting the head and neck region. Also, a revision is done in relation with transmission, the role of saliva, and the pathogenic events associated with human herpesvirus type-8 (HHV-8). Treatment options are revised, highlighting the need for future approaches focused on targeting signaling pathways.

Prospective evaluation of oral mucositis in acute leukemia patients receiving chemotherapy.

PURPOSE: Knowledge of oral mucositis (OM) in patients with acute leukemia (AL) and chemotherapy (CT) has remained limited. Thus, a prospective, longitudinal study was undertaken to characterize clinical features, associated risk factors, and behavior of OM in a cohort of AL patients starting CT. METHODS: Prospective and longitudinal study. A cohort of patients, older than 15 years of age with AL, scheduled to receive CT, was followed from March 2006 to October 2007. At baseline and three times per week, for 21 days, patients had an oral examination performed using the Oral Mucositis Assessment Scale (OMAS); also, oral pain and difficulty to swallow were recorded using a visual analog scale. Weekly, salivary flow measurements (Schirmer's test modified version) were done. RESULTS: A cohort of 29 AL patients was followed for a median time of 21 (range, 14-53) days; 12 (41.4%) developed OM, with a mean OMAS score of 0.181 (SD +/- 0.56) and a mean peak OMAS score of 1.8 (SD +/- 0.56). The OM onset mean time was 9.8 (range, 2-20, SD +/- 6.09) days, with a mean duration of 7 (range, 3-14, SD +/- 4.15) days. OM was significantly correlated with salivary flow [rs = 0.420 (P = 0.0051)], oral pain [rs = 0.47 (P < 0.0001)], ability to swallow [rs = 0.36 (P = 0.0001)], and type of food intake [rs = 0.38 (P < 0.0001)]. CONCLUSIONS: OM is a frequent and early side effect of CT closely correlated with oral pain, difficulty to swallow, and impairment in food intake.

High association of human papillomavirus infection with oral cancer: a case-control study.

BACKGROUND: The aim of the present study was to determine the association of high-risk human papillomavirus (HR-HPV) in Mexican individuals with oral squamous cell carcinoma (OSCC) and their association with various risk factors. METHODS: We designed a matched case-control study. Cases were individuals with newly diagnosed OSCC, age- and sex-matched with controls (1:4). Demographic and clinical data were obtained; also a self-administered questionnaire about sexual behavior was included. DNA from oral brushing was purified to amplify HPV-DNA through MY09/MY11 and GP5+/GP6+ primers and subsequently subjected to sequencing. Conditional regression models were built to calculate odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: Sixty two cases and 248 controls (53.2% males), median age 62 years (Q1-Q3=54-72 years) were included. HPV prevalence was 43.5% in cases and 17.3% in controls (HR-HPV: 37.1% cases, 9.7% controls). The most frequent types in cases were HPV-16 and HPV-18 (55.6 and 18.5%). The presence of HR-HPV was associated with OSCC (OR=6.2; 95% CI: 2.98-12.97) controlling for the most common risk factors. An interaction between smoking and drinking was detected, and family history of cancer was also significant (OR: 3.61; 95% CI=1.44-8.99). Early age at first sexual intercourse and large number of lifetime sexual partners showed an association with HR-HPV (p=0.019 and p=0.033, respectively). CONCLUSIONS: Oral HR-HPV was strongly associated with OSCC, suggesting that HPV-16 and -18 are risk factors for oral cancer in Mexican patients. A significant association of tobacco and alcohol was confirmed. In addition, family history of cancer was associated with OSCC. The results underline the role of HPV in OSCC and its multifactorial etiology.