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.

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.

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.

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.

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.

Ointment Pseudo-Cheilitis: A Disease Distinct From Factitial Cheilitis. A Series of 13 Patients From São Paulo, Brazil.

BACKGROUND: The terms exfoliative cheilitis, factitial cheilitis, and morsicatio labiorum are used to describe self-inflicted lesions of the lip. OBJECTIVE: Here we report and analyze clinical, pathological, and therapeutic data on 13 patients with a form of factitial cheilitis that we believe should be considered a separate entity. RESULTS: Eight patients were male and 5 patients were female. All patients reported pain and presented with crusts consisting of dried saliva and topical medications adherent to the surface of the lips. These patients expressed great concern with their condition, and reported several previous, ineffective treatments. Simple reassurance only was not effective; saline compresses alleviated symptoms for a few patients. Most patients were lost to follow-up. Biopsies were not performed on all patients. CONCLUSION: This particular type of cheilitis artefacta has been previously described, but some features described herein are new and allow a specific approach: patient's behavior, the "protrusion sign," and possible improvement with antidepressants. For these cases, we propose the term ointment pseudo-cheilitis because it comprises the nature of the attached material and the lack of true inflammation. Further psychiatric characterization is a logical next step in further characterizing this difficult-to-treat condition.

A clinicopathological study of the oral lesions of Cowden disease.

BACKGROUND: Cowden disease is a multisystemic cancer predisposition disorder, inherited in an autosomal dominant pattern. Cutaneous and visceral lesions are either malignant tumours or are believed to represent hamartomatous growths. Mucocutaneous lesions are present on almost 100% of affected individuals. Nonetheless, some authors consider that the mucocutaneous manifestations of Cowden disease are, in reality, viral warts at distinct steps of evolution. There are only a few studies regarding the oral manifestations of Cowden disease. OBJECTIVES: To study the oral manifestations of Cowden disease in nine patients clinically and histopathologically. METHODS: The oral mucosal aspects of nine patients with clinical diagnosis of Cowden disease were photographed, and biopsies were taken from typical lesions. RESULTS: All biopsied lesions depicted histopathological aspects suggestive of viral warts at distinct steps of development: incipient, well established and in regression. CONCLUSION: Our findings seem to reinforce the poorly understood hypothesis that the mucocutaneous manifestations of Cowden disease are in reality viral warts. Additional studies are needed to explain why a syndrome caused by the mutation of a tumour suppression gene may cause propensity to warts.

An atrophic, telangiectatic patch at the distal border of the tongue: a mucous membrane manifestation of xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by clinical and cellular sensitivity, pigmentary changes, and early development of malignancies in sun-exposed mucocutaneous and ocular structures due to a defective ability to repair intracellular DNA damage. Individuals with XP also have a greater frequency of oral cancer, particularly squamous cell carcinoma of the anterior third of the tongue. The current study reports four cases of XP that exhibited a characteristic crescent-shaped, atrophic, telangiectatic area on the distal border of the tongue and correlates this lesion with the development of tumors at this site during follow-up. The tongue lesion was photographed and biopsied in the four patients. During routine follow-up visits, new biopsies were performed if additional tongue lesions were observed. The studied lesions were similar in the four patients. During follow-up, squamous cell carcinoma developed in one patient and pyogenic granuloma developed in three patients and was relapsing in one. The lesion remained stable in one patient during the study. The atrophic and telangiectatic patches probably occur because of chronic sun damage to the exposed portion of the tongue, and this area has a high predisposition for the development of benign and malignant tumors.

Adhesion molecules in primary oral mucosal melanoma: study of claudins, integrins and immunoglobulins in a series of 35 cases.

Primary oral mucosal melanoma is a rare aggressive tumor. Recent studies have demonstrated a correlation between increased tumor invasion and the metastatic phenotype and altered adhesion molecule expression profiles. The present study analyzed the expression of integrins, claudins, and immunoglobulin-like adhesion molecules in oral mucosal melanomas and correlated results with clinical parameters. Immunohistochemical analyses of the expression patterns of these molecules were performed on thirty-five cases of primary oral mucosal melanomas organized in a tissue microarray. The results were correlated with clinical and histological features of the cohort. A number of integrin subunits were negative and this was related with vascular invasion. Positivity of integrin beta-3 and CD166 (activated leukocyte cell adhesion molecule) was statistically associated with extensive vascular invasion (P < 0.05). Lower expression of CD54 (intercellular cell adhesion molecule) was associated with cases with extensive necrosis. Most cases with metastatic disease were negative for CD66 (carcinoembryonic antigen-related cell adhesion molecule). Several subunits of claudins were negative and, although not statistically significant, this lack of expression was partially associated with histological factors of poor prognosis. Altered patterns of adhesion molecule expression, mainly integrins and immunoglobulin-like proteins, may participate in the pathogenesis and outcome of oral mucosal melanomas.

Oral lichen planus: case series and experience in a tertiary dermatology service in Brazil.

BACKGROUND: Lichen planus is an inflammatory disease that can affect both the skin and mucous membranes, including the oral mucosa. There is very little original Brazilian dermatology literature about oral lichen planus. OBJECTIVE: To describe the clinical, pathological, and treatment data of 201 patients diagnosed with oral lichen planus followed at the Stomatology Outpatient Clinic of Hospital das Clínicas, Universidade de São Paulo, from 2003 to 2021. METHOD: The patients demographic profile, the morpho-topographic features of the lesions, the treatment employed, and the possible presence of squamous cell carcinoma were analyzed. RESULTS: The disease was more common in women over 50 years of age, tending to be chronic, with a large number of cases showing cicatricial sequelae in the mucosa. Topical treatment with potent corticosteroids was shown to be effective in the vast majority of cases. Squamous cell carcinoma in oral lichen planus cicatricial sequelae was observed in eight cases. STUDY LIMITATIONS: Retrospective study of medical records, with gaps regarding the filling out of data; unequal observation time among the studied cases. CONCLUSIONS: This is the largest Brazilian dermatology series on oral lichen planus. The response to topical corticoid therapy was excellent in the vast majority of cases. The high prevalence of atrophic lesions, demonstrating the chronicity and tissue destruction potential of this disease, may explain the large number of cases of squamous cell carcinoma.

Squamous Cell Carcinoma Arising in Discoid Lupus Erythematosus of the Nail Unit.

Introduction: Discoid lupus erythematosus can affect periungual tissues leading to onychodystrophy. Squamous cell carcinoma can occur in persistent scars of discoid lupus; this rare occurrence has not yet been reported on the nail unit. Case presentation: we report a case of squamous cell carcinoma occurring on the distal phalanx of the thumb in a patient with longstanding periungual discoid lupus on several fingernails. Discussion: Periungual discoid lupus erythematosus is rare. The scars caused by this disease can very rarely develop into squamous cell carcinoma. This is the first report of this occurrence at the periungual tissues.