Non-infectious granulomatous disorders of the upper lip: clinicopathological analysis of 11 patients.

BACKGROUND: Non-infectious granulomatous disorders of the upper lip represent a special chapter of oral and maxillofacial pathology. In this work we report a case-series of this process, to analyse its main clinicopathological features and find differential data that allow us improve its diagnosis and understand its pathogenesis. METHODS: We present 11 cases of non-infectious granulomatous disorders of the upper lip, 8 women and 3 men with an age range of 29-84 years, who have been attended at the Oral Medicine Department of the IUCT (France) and the Oral Medicine Unit of the UPV/EHU (Spain). All clinicopathological data were collected in a specific protocol. RESULTS: We recognized 4 different subtypes of non-infectious granulomatous disorders of the upper lip: (1) associated with Crohn's disease (1 case), (2) associated with foreign body (2 cases), (3) associated with gingivitis lichenoid-like (4 cases), (4) idiopathic (4 cases). CONCLUSIONS: Clinicopathological differences were identified between these subtypes. A good differential diagnosis is necessary in all cases to rule out the presence of local or systemic etiopathogenic factors.

Oral mucosal changes induced by adjuvant endocrine therapies in breast cancer patients: clinical aspects and proposal for management.

Adjuvant systemic treatments in breast cancer are indicated to reduce the risk of relapse. Their systemic side effects have been well documented and include menopausal symptoms such as impaired libido and vaginal dryness, increased risk of endometrial cancer, stroke, musculoskeletal symptoms including arthralgia and myalgia, osteopenia and fractures, skin rashes, and hypercholesterolemia. However, few articles have focused on the oral mucosal reactions related to adjuvant endocrine therapies (AETs) which clearly differ from those reported with chemotherapies or other targeted therapies used for breast cancer. AETs primarily expose patient to a higher risk of worsened periodontal health, salivary flow modifications, taste disturbance, and global deterioration of oral health-related quality of life. Although the rate of permanent discontinuation of AETs because of oral mucosal changes remains low, an interdisciplinary approach to evaluate oral health and to optimize oral supportive care appears essential to ensure an appropriate management and limit dose adjustment in treated patients. In this respect and based on our clinical experience, we propose recommendations to allow oncologists, nurses, and attending practitioners to implement appropriate measures rapidly and/or refer patients to dentists.

No detection of Merkel cell polyomavirus in oral lichen planus: Results of a preliminary study in a French cohort of patients.

Oral lichen planus (OLP) is a chronic inflammatory disease considered as a CD8+ T lymphocyte-mediated autoimmune reaction, which may be triggered by undetermined virus. Recent reports have described the detection of Merkel cell polyomavirus (MCPyV) DNA in oral samples from healthy patients and in patients with different forms of oral cancers. We therefore investigated in a prospective way whether MCPyV was detectable in oral lesions of patients with active OLP. Our preliminary results do not support the hypothesis that OLP may be triggered by MCPyV infection. Further studies are needed to evaluate the involvement of other human polyomaviruses in OLP pathogenesis.

Oral mucosal changes induced by anticancer targeted therapies and immune checkpoint inhibitors.

Development of biological targeted therapies and immune checkpoint inhibitors has redefined the treatment for many cancers; however, the increasing use of new protocols has led to physicians observing a new spectrum of toxicities. To date, oral adverse events induced by these new anticancer therapies have been mainly reported using nonspecific terminology ("stomatitis," "mucosal inflammation," "mucositis") and remain poorly characterized, with the exception of mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis. Oral toxicities of targeted therapies often display very characteristic features which clearly differ from classic oral injuries observed with cytotoxic chemotherapy and/or radiotherapy. In addition, they frequently affect more than 20% of treated patients and can lead to a significant morbidity or permanent treatment discontinuation. Oral mucosal toxicities described in this review include mTOR inhibitor-associated stomatitis (mIAS); stomatitis, benign migratory glossitis, and osteonecrosis of the jaw associated with multi-targeted kinase inhibitors of the VEGF and PDGF receptors; mucositis induced by EGFR inhibitors (in monotherapy or in combination with head and neck radiotherapy and/or chemotherapy); hyperkeratotic lesions with BRAF inhibitors; pigmentary changes and lichenoid reactions secondary to imatinib; and more recent data on the "Osler-Weber-Rendu-like syndrome" described with the antibody-drug conjugate, TDM-1. Finally, we provide, to our knowledge, the first available structured data on oral toxicities induced by the new recently FDA- and EMA-approved monoclonal antibodies targeting PD-1. Clinical management of these targeted therapy-related oral changes is also discussed.

Dermatologic complications of anti-PD-1/PD-L1 immune checkpoint antibodies.

PURPOSE OF REVIEW: The therapeutic use of anti-PD-1/PD-L1 antibodies (nivolumab, pembrolizumab) is rapidly increasing. Given their mechanism of action that triggers T-cell activation, these immune checkpoint inhibitors induce specific adverse events that are mostly of immunologic origin. In this way, cutaneous toxicities represent the most frequent immune-related adverse events (irAEs). The purpose of this review is to summarize the most prevalent dermatologic complications induced by PD-1/PD-L1 immune checkpoint-blocking antibodies and to compare their dermatologic safety profile with anti-CTLA-4 ipilimumab. RECENT FINDINGS: More than 40% of melanoma patients treated with anti-PD-1 therapy are faced with dermatologic irAEs. However, these cutaneous complications usually remain self-limiting and readily manageable. Nonspecific macular papular rash and pruritus represent the most common manifestations. More characteristic lichenoid dermatitis or psoriasis may also develop. Vitiligo is also frequent in patients with melanoma but has not been reported in other types of solid cancers. Mucosal involvement may also occur, including xerostomia and lichenoid reactions. Although available data remain scarce, anti-PD-L1 antibodies present a similar dermatologic safety profile. SUMMARY: Dermatologic irAEs induced by PD-1 or PD-L1 blockade therapy rarely result in significant morbidity or permanent discontinuation of treatment. However, early recognition and appropriate management are crucial for restricting dose-limiting toxicities.

Intensity-modulated radiotherapy for laryngeal and hypopharyngeal cancer: minimization of late dysphagia without jeopardizing tumor control.

PURPOSE: The purpose of this work was to retrospectively determine the value of intensity-modulated radiotherapy (IMRT) in patients with laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC), on outcome and treatment-related toxicity compared to 3-dimensional conformal radiotherapy (3D-CRT). MATERIALS AND METHODS: A total of 175 consecutive patients were treated between 2007 and 2012 at our institution with curative intent RT and were included in this study: 90 were treated with 3D-CRT and 85 with IMRT. Oncologic outcomes were estimated using Kaplan-Meier statistics; acute and late toxicities were scored according to the Common Toxicity Criteria for Adverse Events scale v 3.0. RESULTS: Median follow-up was 35 months (range 32-42 months; 95% confidence interval 95%). Two-year disease-free survival did not vary, regardless of the technique used (69% for 3D-CRT vs. 72%; for IMRT, p = 0.16). Variables evaluated as severe late toxicities were all statistically lower with IMRT compared with 3D-CRT: xerostomia (0 vs. 12%; p < 0.0001), dysphagia (4 vs. 26 %; p < 0.0001), and feeding-tube dependency (1 vs 13%; p = 0.0044). The rates of overall grade ≥ 3 late toxicities for the IMRT and 3D-CRT groups were 4.1 vs. 41.4%, respectively (p < 0.0001). CONCLUSION: IMRT for laryngeal and hypopharyngeal cancer minimizes late dysphagia without jeopardizing tumor control and outcome.

"Plasma cell gingivitis" encompasses multiple entities: a retrospective series of 37 cases.

BACKGROUND: Plasma cell gingivitis is defined as gingival inflammation comprised of plasma cell infiltrates. This diagnostic criterion is non-specific and underlying mechanisms remain unknown. OBJECTIVES: We performed a multidisciplinary clinico-pathological review of cases previously identified as "gingivitis with plasma cell infiltrates", with assessment of putative contributing factors and critical appraisal of the final diagnosis. MATERIALS & METHODS: Cases previously identified as "gingivitis with plasma cell infiltrates" between 2000 and 2020 were included from archives from the GEMUB group, a French multidisciplinary network of physicians with expertise on oral mucosa. RESULTS: Among the 37 included cases, multidisciplinary clinico-pathological review allowed differential diagnosis in seven cases (oral lichen planus n=4, plasma cell granuloma n=1, plasmacytoma n=1, and mucous membrane pemphigoid n=1). The remaining cases were classified as "reactive plasma cell gingivitis" (induced by drugs, trauma/irritation or periodontal disease) (n=18) or "idiopathic plasma cell gingivitis" when no contributing factors were identified (n=12). Clinico-pathological characteristics did not differ significantly between "reactive" and "idiopathic" cases, preventing us from identifying specific features of "idiopathic" plasma cell gingivitis. CONCLUSION: "Plasma cell gingivitis" is a polymorphous, non-specific entity with various aetiologies, of which the diagnosis requires multidisciplinary anatomo-clinical correlation for exclusion of secondary causes of plasma cell infiltration. Although our study was limited by its retrospective design, most cases of "plasma cell gingivitis" appeared to be associated with an underlying cause. We propose a diagnostic algorithm to properly investigate such cases.

Smartphone oral self-photography in teledentistry: Recommendations for the patient.

In the current context of the coronavirus disease 2019 pandemic, the deployment of telemedicine has accelerated considerably. Like telemedicine, teledentistry involves the use of telecommunication technologies to provide medical information and services. Teledentistry can contribute to remote assessment (teletriage) and continuity of care (telemonitoring). This evaluation at a distance can be done by sending photos taken by the patient with a smartphone. Providing patients with a simple and reproducible protocol and explaining how to take a photo is important for sufficient image quality. The aim of this technical note is to help clinicians advise their patients on how to take photographs of their oral cavity simply and with sufficient quality to be reproducible.

Oral acute graft versus host disease after donor lymphocyte infusions: Clinicopathological characterization in a monocenter cohort.

Donor lymphocyte infusions (DLI) are used after hematopoietic stem cell transplant (HSCT) in order to boost the graft-versus-tumor effect. The most significant toxicity is acute or chronic graft-versus-host disease (GVHD), whose clinical symptoms mirror those occurring after HSCT. By contrast, oral acute GVHD lesions have been exceptionally described post-DLI. We report on a monocenter cohort of 12 adult patients that developed oral acute GVHD after DLI. The majority was treated for acute myeloid leukemia. A total of 29 DLI treatments were applied and the median time between the last DLI and the oral mucosal lesions was 42 days. Most patients presented these oral lesions concomitant with skin lesions and none of them had exclusive oral involvement. Oral lichenoid changes were observed in 11 patients, including plaque-like lesions and/or reticulated white streaks consistent with Wickham's striae, affecting mainly the buccal mucosa and dorsal or lateral aspects of the tongue. Mucosal histopathological findings showed a patchy-to-florid lichenoid interface dermatitis for 3 biopsied patients. Eight patients also experienced salivary gland changes. The treatment of oral lesions included high- to very high-potency topical corticosteroids in the majority of patients. Oral GVHD lesions have seldom been described after DLI, and only exceptionally in an acute setting. Our results are not consistent with those reported in the literature evaluating GVHD after DLI. In fact, oral acute GVHD lesions post-DLI appeared very common and similar to the oral lichenoid reactions of chronic GVHD following HSCT. The main limitations of this work are its retrospective design and the relatively small sample size.

Dermatological Toxicities of Bruton's Tyrosine Kinase Inhibitors.

The development of Bruton's tyrosine kinase (BTK) inhibitors represents a major breakthrough in the treatment of chronic lymphocytic leukemia and other B cell malignancies. The first-generation inhibitor ibrutinib works by covalent irreversible binding to BTK, a non-receptor tyrosine kinase of the TEC (transient erythroblastopenia of childhood) family that plays a critical role in the B-cell receptor signaling pathway. It also induces an 'off-target' inhibition of a range of other kinases including (but not limited to) epidermal growth factor receptor (EGFR), SRC, and other kinases of the TEC family (interleukin-2-inducible T-cell kinase [ITK], Tec, BMX). Dermatological toxicities are among the most common toxicities of ibrutinib, but remain of mild to moderate intensity in most cases and are readily manageable. Their incidence is highest during the first year of treatment and declines over time. In addition, it has been postulated that ibrutinib-related dermatologic adverse events are mediated by the direct binding to both BTK and other 'off-target' kinases. Bruising, ecchymoses, and petechiae represent the most characteristic dermatologic adverse events. Nail and hair changes are also common, as skin infections (opportunistic infections including herpes simplex and herpes zoster virus reactivations, and Staphylococcus aureus superinfection), folliculitis, and other types of rashes. Panniculitis, aphthous-like ulcerations with stomatitis, neutrophilic dermatosis, peripheral edema, and skin cracking can also occur. Next-generation BTK inhibitors, acalabrutinib and zanubrutinib, have been designed to optimize BTK inhibition and minimize off-target inhibition of alternative kinases (Tec, ITK, EGFR, SRC-family kinases). These drugs have been recently FDA-approved for relapsed or refractory mantle cell lymphoma. Although the overall incidence of their toxicities is expected to be more limited, acalubrutinib and zanubrutinib are associated with a range of dermatologic toxic effects that appear to be similar to those previously described with ibrutinib, including bruising and ecchymoses, panniculitis, human herpesvirus infections, cellulitis, and skin rash. In particular, both drugs induce skin bleeding events in more than 30% of patients treated. However, the available dermatological data are still rather limited and will have to be consolidated prospectively. This review article analyses the wide spectrum of dermatological toxicities that can be encountered with first- and second-generation BTK inhibitors. Finally, recommendations for appropriate treatment as well as a synthesis algorithm for management are also proposed.

[Oral complications following allogeneic hematopoietic cell transplantation: Recommendations of the Francophone Society of Bone Marrow transplantation and cellular Therapy (SFGM-TC)]. / Complications stomatologiques dans le contexte de l'allogreffe de cellules hématopoïétiques : recommandations de la Société francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC).

Stomatological complications of allogeneic hematopoietic stem cell transplantation (HSCT) are frequent and very uncomfortable for patients. The primary complication is the graft versus host disease reaction. Other side effects of the procedure include infections, taste disorders and carcinogenic risks. Various local treatments are used but remain imperfect. Within the framework of the 10th workshop of practice harmonization of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held in Lille in September 2019, diagnostic approaches and treatments of tongue and oral complications following allogeneic HSCT were reviewed according to the analysis of published studies.

Geographic stomatitis with palate involvement.

Benign migratory glossitis or geographic tongue is a benign condition that usually manifests as asymptomatic erythematous and migratory circinate patches, involving the lateral and dorsal aspects of the tongue. Extra-lingual lesions uncommonly occur and are mainly located on labial and buccal mucosae, lips and floor of the mouth. The present report describes one patient with a geographic lesion on the hard palate associated with lingual lesions and another patient who had multiple geographic lesions both in the hard and soft palate without lingual lesions. We found 64 cases in the English literature of ectopic locations with 22 palate involvement. No case of simultaneous involvement of the hard and the soft palate was found.

Dental screening of medical patients for oral infections and inflammation: consideration of risk and benefit.

The primary purpose of preoperative dental screening of medical patients is to detect acute or chronic oral conditions that may require management prior to planned medical interventions. The aim of this communication is to discuss the background of preoperative dental screening and the link between dental pathologies and systemic diseases.