Histopathologic findings in ointment pseudo-cheilitis: An alert to dermatopathologists.

Ointment pseudo-cheilitis is a recently recognized distinctive type of self-induced cheilitis. Lesions consist of a variable amount of crusts adhered to the vermilion. These crusts consist of dried saliva and dead cells mixed with applied medications attached to the lip surface. Patients are typically severely anxious or depressed; the condition impacts quality of life. Ointment pseudo-cheilitis is frequently misdiagnosed as exfoliative cheilitis or cheilitis glandularis. Biopsy reports are often non-revealing because there are no established histopathological criteria for this disease, and clinicians usually do not formulate the correct diagnostic hypothesis. Here, we present the histopathological findings of four cases of ointment pseudo-cheilitis. The most consistent finding was the presence of laminated parakeratotic material detached from the epithelium in biopsies that are devoid of other significant diagnostic changes. This material at the lip surface possibly represents physiologic labial desquamation mixed with dried saliva and applied medication. With this report, we intend to alert dermatopathologists to the diagnosis of ointment pseudo-cheilitis if they receive biopsies from patients who present clinically exuberant labial lesions that show only minimal histopathological changes.

Oral lupus erythematosus: Immunohistochemical evaluation of CD1a, CD21, CD123, and langerin expression in dendritic cells.

BACKGROUND: Dendritic cells participate in the pathophysiology of lupus erythematosus (LE), which are studied in systemic and cutaneous forms; however, little is known about their oral manifestations. METHODS: The expressions of dendritic cell markers (including CD1a, CD21, CD123, and langerin) were investigated by immunohistochemistry technique. Sixty intraoral and lower lip LE lesions, and additional 10 control samples were collected from 2003 to 2019. They were topographically analyzed in the epithelium (EP), lamina propria (LP), epithelial junction (JUN), and deep perivascular (PV) areas. RESULTS: The expression of CD1a was decreased in the EP (p = 0.003) and increased in the deep PV area (p = 0.002). Langerin immunostaining showed no significant decrease in EP (p = 0.944); however, it increased in LP (p = 0.012) and JUN (p = 0.006). CD21 was expressed in only two specimens (EP, p = 0.012; LP, p < 0.001; deep PV area, p = 0.018). CD123 expression increased in all topographies (EP, p < 0.005; LP, p < 0.001, JUN, p < 0.001; deep PV, p < 0.001). The comparison between vermilion and intraoral mucosa LE lesions suggested that sun-exposed sites showed higher expression of CD123 (EP, p = 0.024; LP, p = 0.047; JUN, p = 0.001). CONCLUSIONS: CD1a, langerin, and CD123 expressions were detected coincidently surrounding the inflammatory infiltrate in oral LE, suggesting that these cells may play an important role in immune response. Interestingly, plasmacytoid dendritic cells showed increased CD123 expression in sun-exposed site lesions, which point out a possible function in their pathogenesis. Further studies are needed to confirm this hypothesis.

An update on viral-induced cutaneous lymphoproliferative disorders. CME Part I.

Viral-induced cutaneous T-cell lymphomas are an uncommon group of lymphoproliferative disorders characterized by a viral infection of T and natural killer (NK) cells. This group of cutaneous T-cell lymphomas is more commonly encountered in Asians and Native Americans from Central and South America compared with Western populations. Viral-associated lymphoproliferative disorders include a spectrum of entities that range from nonneoplastic lesions, such as chronic active Epstein-Barr virus infection and infective dermatitis to malignant diseases, such as extranodal NK/T-cell lymphoma, hydroa vacciniforme-like T-cell lymphoma, and adult T-cell leukemia/lymphoma. This review article will focus on hydroa vacciniforme-like lymphoproliferative disorder, extranodal NK/T-cell lymphoma, adult T-cell leukemia/lymphoma, lymphomatoid granulomatosis, and Epstein-Barr virus-positive mucocutaneous ulcers. We will review the pathogenesis of these conditions and the challenges of making a timely diagnosis in early-stage disease and discuss the common clinicopathologic manifestations, mutational landscape, and approaches to treat these highly aggressive and frequently lethal types of lymphoma.

Three cases of oral mucosal tuberculosis in patients on tumour-necrosis-factor-α blockers.

We present three cases of oral mucosal lesions caused by Mycobacterium tuberculosis in patients treated with anti-tumour necrosis factor-α for psoriasis or rheumatoid arthritis. Diagnosis of oral mucosal tuberculosis was not easily established in any of the cases. A comparison between these cases and other previously described forms of oral mucosal tuberculosis is presented.

EMT in salivary gland tumors: the expression of microRNAs miR-155 and miR-200c is associated with clinical-pathological parameters.

BACKGROUND: Epithelial to mesenchymal transition promotes cell adhesion loss, enabling invasion and metastasis. MicroRNAs are a class of small non-codifying RNAs that regulate gene expression. OBJECTIVES: The aim of this study was to evaluate the expression of microRNAs that could regulate the expression of EMT factors in salivary gland tumors (SGTs). METHODS AND RESULTS: The expression of microRNAs miR-9, miR-34a, miR-101, miR-138, miR-155, and miR-200c-described in the literature to target EMT factors-was evaluated by Real-time RT-PCR (qPCR) in pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) samples. Bioinformatics tools were applied to identify miR targets and immunohistochemistry was used to examine the expression of the proteins E-cadherin, Twist, ZEB-1, ß-Catenin, and c-Kit. Comparing miR expression among SGT types, we observed increased expression of miR-9, and miR-138 in PAs, and increased miR-155 expression in MECs. Low-grade MECs exhibited increased miR-155 expression (p = 0.032). MECs that generated lymph node metastases had increased miR-200c levels (p = 0.018). MECs tended to have decreased expression of EMT-related proteins when compared to the other SGT types (c-Kit p < 0.001, Twist p = 0.014, and ZEB p = 0.012). Notably, increased c-Kit expression was associated with the presence of perineural infiltration in ACC (p = 0.050). CONCLUSIONS: This study provides evidence of alterations in the expression of EMT-factors regulating miRs, especially of miR-9, miR-138, miR-155, and miR-200c. No significant relationships were found between the expression of these miRs and proteins associated with EMT in SGTs.

Prevalent Transmission of 'Candidatus Liberibacter asiaticus' over 'Ca. Liberibacter americanus' in a Long-Term Controlled Environment.

In Brazil, citrus huanglongbing (HLB) is associated with 'Candidatus Liberibacter americanus' (CLam) and 'Ca. Liberibacter asiaticus' (CLas). However, there are few studies about HLB epidemiology when both Liberibacter spp. and its insect vector, the Asian citrus psyllid (ACP, Diaphorina citri), are present. The objective of this work was to compare the transmission of HLB by ACP when both CLam and CLas are present as primary inoculum. Two experiments were performed under screenhouse conditions from April 2008 to January 2012 (experiment 1) and from February 2011 to December 2015 (experiment 2). The experiments were carried out with sweet orange plants infected with CLam or CLas as inoculum source surrounded by sweet orange healthy plants. One hundred Liberibacter-free adult psyllids were monthly confined to the source of inoculum plants for 7 days with subsequent free movement inside the screenhouse. Fortnightly, nymphs and adults of psyllids were monitored. Psyllid and leaf samples were collected periodically for Liberibacter detection by PCR or quantitative PCR. CLas was detected more frequently than CLam in both psyllid and leaf samples. No mixed infections were detected in the psyllids. A clear prevalence of CLas over CLam was observed in both experiments. The final HLB incidences were 16.7 and 14.5% of Liberibacter-positive test plants, and CLas was detected in 92.3 and 93.1% of these infected plants. Mixed infection was observed only in 3.8% of infected test plants in experiment 1. These results endorse the shift in the prevalence of CLam to CLas observed in citrus orchards of São Paulo, Brazil.

The Role of Reflectance Confocal Microscopy in the Evaluation of Pigmented Oral Lesions and Their Relationship With Histopathological Aspects.

ABSTRACT: Oral pigmentations are a heterogeneous group and can be the result of physiological activity of oral mucosal melanocytes, secondary to exogenous causes, associated with systemic or local diseases, or due to proliferative activity of melanocytes. Their diagnosis is critical because these lesions can be markers of internal diseases or, in the case of melanocytic proliferative processes, they may represent a malignant neoplasm. In the past decade, the use of reflectance confocal microscopy, a noninvasive imaging tool, has aided the analysis of such lesions, but the establishment of firm criteria in their evaluation is still lacking. This study evaluated a series of 19 cases of pigmented oral lesions and correlated the reflectance confocal microscopy findings with histopathological classical criteria. We found 13 cases of melanotic macule, 1 of them associated with Peutz-Jeghers syndrome and 2 with Laugier-Hunzinker syndrome; 1 melanocytic nevus; 2 lentigo maligna; 2 pigmented actinic cheilitis; and 1 case of postinflammatory pigmentation secondary to a lupus erythematosus oral discoid lesion. The main difference between benign and malignant lesions was the presence of atypical proliferation in lentigo maligna. Langerhans cells with thick dendritic processes, which may be present in other benign and inflammatory pigmentations is one of the main reasons for diagnostic pitfalls.

Metastasis to the Oral Cavity: Report of 12 Cases.

ABSTRACT: Oral cavity is not a common route for metastatic dissemination; metastasis to the oral region may affect soft tissues and jawbones, accounting for approximately 1% of all oral malignant neoplasms. The diagnosis of metastatic lesions to the oral cavity is usually challenging to clinicians and pathologists because of their complexity and rarity. We present a series of 12 metastatic neoplasms to the oral cavity that were detected previously or after the diagnosis of the primary tumor. All tumors were of epithelial origin with primary sites in the esophagus (2 cases), colon (2 cases), bladder, lungs, liver, larynx, skin, uterus, prostate, and adrenal gland, each with one case. The commonest site of the metastatic masses in the oral cavity was the gingiva, frequently presented as a vegetating, friable mass. The clinical examination and histopathologic analysis of the lesions were central to establishing the final diagnosis of the tumors. Metastatic masses to the oral cavity should always be considered as differential diagnosis of benign-looking lesions, especially in patients with previous history of a malignant disease. Biopsy is mandatory to establish an accurate diagnosis.

Actionable Mutation Profile of Sun-Protected Melanomas in South America.

ABSTRACT: Melanomas that arise in sun-protected sites, including acral and oral mucosal melanomas, are likely under the control of unique, specific mechanisms that lead to mutagenesis through various pathways. In this study, we examined somatic mutations in tumors by targeted sequencing using a custom Ion Ampliseq Panel, comprising hotspots of 14 genes that are frequently mutated in solid tumors. Tumor DNA was extracted from 9 formalin fixation, paraffin-embedded sun-protected melanomas (4 primary oral mucosal melanomas and 5 acral lentiginous melanomas), and we identified mutations in the NRAS , PIK3CA , EGFR , HRAS , ERBB2 , and ROS1 genes. This study reveals new actionable mutations that are potential targets in the treatment of photo-protected melanomas. Additional studies on more of these melanoma subtypes could confirm our findings and identify new mutations.

In Vivo Reflectance Confocal Microscopy of Adnexal Tumors: Evaluation of Trichoepithelioma, Sebaceoma, and Fibrofolliculoma.

ABSTRACT: Cutaneous adnexal tumors are benign and malignant neoplasms that undergo morphological differentiation into cutaneous adnexa, comprising pilosebaceous, eccrine, or apocrine units. Reflectance confocal microscopy is a noninvasive diagnostic method that enables in vivo visualization of tissues at a similar resolution as conventional histopathology. The use of this method in skin imaging over the past several years has improved dermatological diagnoses, potentiating its wide application, especially for benign and malignant skin tumors. We describe the use of reflectance confocal microscopy in cases of trichoepithelioma, sebaceoma, and fibrofolliculoma and correlate the resulting clinical, histopathological, and confocal microscopy images.

Extraordinary Case: Unique Presentation of an Aggressive Epstein-Barr Virus-Positive Mucocutaneous Ulcer.

ABSTRACT: Epstein-Barr virus-positive mucocutaneous ulcer is a recent and unusual type of lymphoproliferation, mostly associated with various forms of immunosuppression. In most cases, they regress spontaneously, but an increasing number of reports describe a spectral behavior of the lesion, which ranges from a simple ulcer with eosinophilia to aggressive ulcers. In these cases, Epstein-Barr virus-related lymphomas are the main differential diagnosis. We report a unique observation of this rare disease with mandibular involvement. Due to bone erosion, the patient was treated with 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) with complete healing of the ulcer on clinical examination and PET-scan control.

Characteristics of aquaporin 1, 3, and 5 expression during early murine salivary gland development.

Aquaporins (AQPs) are essential to coordinate the transit of water and ions through the cell membrane. In salivary glands (SGs), AQPs have been associated with saliva formation, facilitating water absorption through the epithelium during the formation of hypotonic saliva, which is then secreted into the oral cavity. Different members of the AQP family have been suggested to play distinct roles during embryonic development, highlighted by their specific expression patterns. Here, we have investigated the expression patterns of AQP-1, AQP-3 and AQP-5 by immunofluorescence at key stages of salivary gland development, utilising cultured mouse embryonic submandibular (SMG) and sublingual (SLG) glands. The expression of AQPs was compared to a mitotic marker, phospho-histone 3 (PH3), a myoepithelial marker, smooth muscle actin (SMA), and a vascular marker, CD31. Qualitative analysis revealed that AQP-1 and AQP-3 were primarily expressed during the earlier phases of SG morphogenesis and were associated with cells undergoing mitotic processes (PH3-positive). AQP-5, in contrast, was not associated to mitotic figures, but was predominantly expressed during late stages of SG morphogenesis. Our results highlight that AQPs are expressed from early stages of SG morphogenesis and exhibit complimentary expression patterns that may contribute to the morphogenesis of salivary glands.

Orofacial Granulomatosis and Crohn Disease: Coincidence or Pattern? A Systematic Review.

BACKGROUND: To systematically review all cases of orofacial granulomatosis (OFG) and evaluate the association between OFG and Crohn disease (CD). SUMMARY: This review was conducted according to PRISMA guidelines and a search of the PubMed, MEDLINE, and Embase databases, and the Cochrane Library in March 2020, using keywords and MeSH terms associated with "orofacial granulomatosis," "Crohn disease," and their variants, with no language restrictions and across all age groups. All relevant articles were accessed in full text. Single case reports and articles on sarcoidosis, allergy, ulcerative colitis, and infectious diseases were excluded from the analysis. RESULTS: We retrieved 507 reports on OFG. The mean age at onset was 23.3 years (range 2-89 years). A total of 240 (47.3%) females and 267 (52.6%) males were included. CD was present in 93 children aged <16 years (68.3%) and in 43 adults (31.9%). In most cases, the OFG appeared before the CD. The most common clinical manifestations were intraoral mucosa abnormalities (n = 251; 49.5%), lower-lip swelling (n = 249; 49.1%), upper-lip swelling (n = 227; 44.7%), and gingivae (n = 193; 38.7%). Patients with concurrent CD were more likely to experience involvement of the buccal sulcus. Key Messages: OFG presents primarily as a solo entity. The OFG that was associated with CD was present in 93 children aged under 16 years (68.3%) and in 43 adults (31.9%). Childhood onset of OFG carries with it a higher risk of developing CD.

Clinical Profile of Melkersson-Rosenthal Syndrome/Orofacial Granulomatosis: A Review of 51 Patients.

BACKGROUND: Melkersson-Rosenthal syndrome (MRS) is a rare disease characterized by the triad of granulomatous cheilitis, fissured tongue, and facial paralysis. Publications concerning large series are rare in the literature. OBJECTIVES: To describe the clinical and histopathological characteristics of patients with complete and oligosymptomatic forms of MRS. METHODS: A retrospective records review was performed for the diagnoses of Melkersson-Rosenthal syndrome, granulomatous cheilitis, and orofacial granulomatosis at oral Diseases Clinic of the Department of Dermatology, University of São Paulo, Brazil (2003, 2017). RESULTS: A total of 51 patients were included, mean age at presentation 35.69 years. Four patients were younger than 18 years. The complete triad of was observed in 10 patients. The rare findings of granulomatous blepharitis, gingivitis and palatitis are presented. Comorbidities included Crohn's disease (5 patients), migraine headaches (1 patient) and convulsions (2 patients). Granulomatous inflammatory infiltrate was detected in 31 biopsies. Medical therapies included included oral and intralesional steroids, thalidomide, dapsone, azathioprine, tetracycline, methotrexate, and surgery, with variable responses. CONCLUSIONS: Our report meant to draw attention to the clinical spectrum of this rare disorder, mainly to oligosymptomatic forms and rarer presentations.

Oral Squamous Cell Carcinoma Bone Invasion: Possible Roles of E-Cadherin in Osteoclastogenesis and Bone Infiltration.

INTRODUCTION: Squamous cell carcinoma is the most common cancer of the oral cavity. When the tumor invades the bone tissue, the prognostic and survival rates decrease a lot, and the treatment becomes more aggressive, with several damages to the patient and health system. Many of the molecular mechanisms of bone invasion process are not understood yet, but it is already known that one of central processes of tumor evolution - adjacent tissues invasion and metastasis - is a large spectrum of phenotypic changes in epithelial cells to mesenchymal, in a process named as epithelial-mesenchymal transition (EMT). Loss of E-cadherin, an important epithelial cell adhesion protein, is a hallmark of this phenomenon. The objective of this retrospective study is to evaluate the expression of E-cadherin protein, comparing its distribution with clinical characteristics of the patients and possibly relation to EMT. METHODS: Sixty-two cases with respective clinical data were analyzed by comparing immunohistochemical, H and E staining, and clinical data, observing the tumor-bone interface (TBI) and the surrounding tumor that had no direct contact with the bone surface (ST). RESULTS: Forty cases were positive for E-cadherin (64%) with a heterogeneous pattern. Statistical analysis showed a significant difference between the presence of E-cadherin expression and tobacco smokers. Also, the equal or weaker protein expression in the ST than TBI is related to a worse overall survival. No statistically significant difference in other prognostic factors was observed. CONCLUSION: Our results suggest that the tumor cells that interact with the bone tissue could gain molecular changes, like partial EMT and osteoclastogenesis induction, which facilitate their migration and increase the bone resorption, resulting in a worse patient's prognosis.

Influence of the Storage in Bottle on the Antioxidant Activities and Related Chemical Characteristics of Wine Spirits Aged with Chestnut Staves and Micro-Oxygenation.

Different ageing technology of wine spirits (WSs) has been investigated, but little has been published on the chemical evolution of aged WS during storage in bottle. The purpose of this study was to examine how 12 months of storage in bottle affected the evolution of antioxidant activity (DPPH, FRAP and ABTS assays), total phenolic index (TPI) and low molecular weight (LMW) compounds content of the WSs aged through alternative technology using three micro-oxygenation levels (MOX) and nitrogen control (N). Results revealed the ability of phenolic compounds from aged WSs to scavenge free radicals during storage in bottle. Among the in vitro antioxidant-activity methods, FRAP assay was the more effective to differentiate WSs according to the ageing technology. Concerning the overall influence of storage in bottle on antioxidant activity, and TPI and LMW compounds content, the higher results were obtained for the MOX modalities (O15, O30 and O60), which showed a similar evolution. In summary, this study provides innovative information, demonstrating that the differences between the aged WSs imparted throughout the ageing process (resulting from different MOX levels) were mostly retained, and only slight modifications during storage in bottle were found.

In vivo confocal microscopy of dermoscopic suspicious lesions in patients with xeroderma pigmentosum: A cross-sectional study.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare genetic disease characterized by extreme photosensitivity, resulting in a higher incidence of cutaneous tumors. Reflectance confocal microscopy (RCM) is a noninvasive imaging method for diagnosing cutaneous lesions. OBJECTIVE: To explore the application of RCM in the follow-up of patients with XP. METHODS: Patients with XP underwent RCM for suspicious lesions from January 2010 through April 2019. Lesions with malignant RCM features were excised, and the results were compared with their histopathologic features. Benign lesions on RCM were monitored every 3 months. We recorded the confocal features that were related to malignancy and specifically to melanoma. RESULTS: A total of 61 suspicious lesions from 13 patients with XP were included. Thirty-three lesions (54%) were malignant (14 melanomas, 15 basal cell carcinomas, and 4 squamous cell carcinomas). Nonvisible papillae (OR, 11.8; 95% CI, 2.6-53.1; P = .001) and atypical cells at the dermoepidermal junction (OR, 11.7; 95% CI, 2.7-50.3; P = .001) were independent predictors of malignancy. LIMITATIONS: There were limited numbers of patients and lesions. Most cases were retrospectively included, and some did not have a histologic analysis. CONCLUSIONS: RCM is a valuable tool in the follow-up of patients with XP, reducing the need for excisions by 35%.

From strawberry gingivitis to palatal perforation: The clinicopathological spectrum of oral mucosal lesions in granulomatosis with polyangiitis.

BACKGROUND: Reports of oral manifestations of granulomatosis with polyangiitis (GPA) usually refer to single-case reports; "strawberry gingivitis" has been increasingly reported. OBJECTIVE: To study the clinicopathological findings of four patients in which the diagnosis of GPA was suspected from the observation of their oral lesions and compare these to existent data. METHODS: Retrospective study of a case series. RESULTS: One patient presented typical "strawberry gingivitis" with localized disease and negative ANCA results. Two patients presented rapidly growing oral ulcers associated with systemic compromise and high ANCA levels. One patient presented with a chronic granulomatous lesion that leaded to palatal perforation. CONCLUSION: Oral manifestations of GPA may vary from rapidly evolving lesions in acutely ill patients to chronic and locally destructive lesions in slowing developing disease. These differences are also evident in the histopathological findings.

The histopathological spectrum of Melkersson-Rosenthal syndrome: Analysis of 47 cases.

BACKGROUND: Melkersson-Rosenthal syndrome (MRS) is a rare disease characterized by the triad of recurrent orofacial edema, relapsing facial paralysis and plicated tongue. Histopathological features of MRS have not been extensively analyzed. METHODS: This study investigated the histopathological aspects of oral lesions from 47 MRS patients. RESULTS: The most common biopsy site was the upper lip, followed by the lower lip, gingiva and palate. The most important findings were ill-defined and well-formed granulomas. Lymphoplasmacytic inflammatory infiltrate was seen in early and late stages of MRS. Edema, fibrosis, vasodilatation and congestion were the most common finding in the lamina propria. Gingival and palate exams also demonstrated granulomatous infiltrates. Regarding the evolution time of the disease, we demonstrated that, in initial phases, there is a lymphoplasmacytic inflammatory infiltrates, followed by a granulomatous infiltrate and, subsequently, fibrosis. CONCLUSION: Histopathological examination of oral lesions is helpful for the diagnosis of MRS; the absence of granulomatous inflammation does not exclude the diagnosis of syndrome. Clinical and histopathological analysis of the rare gingival and palate lesions is important, since all histopathological findings of the disease were detected in these sites.

Distinct Salivary Gland Features in Sjögren's Syndrome and Lupus Erythematosus Sialadenite.

BACKGROUND: Primary Sjögren's syndrome (pSS) is an important cause of xerostomia, and the presence of this symptom in lupus erythematosus (LE) is usually referred to as secondary SS. Although these diseases share many clinical and laboratory aspects, the histopathological changes of minor salivary glands (MSG) have been widely evaluated to determine whether this damage is specific for each disease. Based on this query, the aim of this study was to analyze morphological findings of minor salivary glands in pSS or LE. METHODS: Two groups of 30 (MSG) from patients with pSS and LE were histopathologically evaluated, and the results were statistically analyzed using the two-tailed Fisher exact test. RESULTS: The morphological changes were distinct among the groups and statistically significant. In pSS, the most evident features were the focal lymphocytic ductal aggression, with the focus score ≥1 and the periductal fibroplasia, while in LE, perivascular inflammatory infiltrate, spongiosis of ductal cells not associated with the exocytosis, and hyalinization of the periductal basement membrane were detected. CONCLUSIONS: These results indicated that in each disorder, MSG have their specific morphological changes, which lead to xerostomia, and the impairment of MSG in LE is probably due to a lupus sialadenitis.