Epithelial-derived interleukin-23 promotes oral mucosal immunopathology.

At mucosal surfaces, epithelial cells provide a structural barrier and an immune defense system. However, dysregulated epithelial responses can contribute to disease states. Here, we demonstrated that epithelial cell-intrinsic production of interleukin-23 (IL-23) triggers an inflammatory loop in the prevalent oral disease periodontitis. Epithelial IL-23 expression localized to areas proximal to the disease-associated microbiome and was evident in experimental models and patients with common and genetic forms of disease. Mechanistically, flagellated microbial species of the periodontitis microbiome triggered epithelial IL-23 induction in a TLR5 receptor-dependent manner. Therefore, unlike other Th17-driven diseases, non-hematopoietic-cell-derived IL-23 served as an initiator of pathogenic inflammation in periodontitis. Beyond periodontitis, analysis of publicly available datasets revealed the expression of epithelial IL-23 in settings of infection, malignancy, and autoimmunity, suggesting a broader role for epithelial-intrinsic IL-23 in human disease. Collectively, this work highlights an important role for the barrier epithelium in the induction of IL-23-mediated inflammation.

Neutrophil extracellular traps and extracellular histones potentiate IL-17 inflammation in periodontitis.

Neutrophil infiltration is a hallmark of periodontitis, a prevalent oral inflammatory condition in which Th17-driven mucosal inflammation leads to destruction of tooth-supporting bone. Herein, we document that neutrophil extracellular traps (NETs) are early triggers of pathogenic inflammation in periodontitis. In an established animal model, we demonstrate that neutrophils infiltrate the gingival oral mucosa at early time points after disease induction and expel NETs to trigger mucosal inflammation and bone destruction in vivo. Investigating mechanisms by which NETs drive inflammatory bone loss, we find that extracellular histones, a major component of NETs, trigger upregulation of IL-17/Th17 responses, and bone destruction. Importantly, human findings corroborate our experimental work. We document significantly increased levels of NET complexes and extracellular histones bearing classic NET-associated posttranslational modifications, in blood and local lesions of severe periodontitis patients, in the absence of confounding disease. Our findings suggest a feed-forward loop in which NETs trigger IL-17 immunity to promote immunopathology in a prevalent human inflammatory disease.

Blastoid Mantle Cell Lymphoma of the Palate: Report of a Rare Aggressive Entity and Review of the Literature.

Mantle cell lymphoma (MCL) is a well-defined, non-Hodgkin lymphoma of B-cell origin displaying diverse morphological phenotypes and variable disease course. The World Health Organization recognizes two aggressive histopathologic variants of this type of lymphoma: pleomorphic and blastoid MCL. To date, only few cases of MCL affecting the oral cavity have been reported. Additionally, the involvement of the oral and maxillofacial area by aggressive MCL subsets is considered extremely rare with only two patients reported in the English language literature to the best of our knowledge. Herein, we describe a 69 year-old male with a prior history of MCL of the right lateral pharyngeal wall developing a recurrent lesion extending to the palatal mucosa as diffuse ulceration and exhibiting histomorphological features of blastoid MCL. We also review the pertinent literature with emphasis on the diagnostic challenges and distinction between the different MCL variants.

Lymphoepithelial Subtype of Oral Squamous Cell Carcinoma: Report of an EBV-Negative Case and Literature Review.

Lymphoepithelial carcinoma (LEC) of the oral mucosa is a rare histopathologic subtype of squamous cell carcinoma (SCC), which shares morphologic similarities with nasopharyngeal carcinoma (NPC), non-keratinizing undifferentiated subtype. The admixture of neoplastic epithelial tumor cells and a dense lymphoplasmacytic infiltrate makes microscopic diagnosis challenging. LEC etiopathogenesis has been variably associated with Epstein-Barr virus (EBV) infection, depending on the specific anatomic location and racial predilection, with a higher incidence in endemic populations. Although described in several subsites of the head and neck region, including the major salivary glands, the oral mucosa is considered an infrequent location for LEC development, deriving either from minor salivary glands (MSGs) or the surface epithelium. Herein, we report a rare case of an EBV-negative LEC arising from the oral surface epithelium, presenting as gingival swelling, and review the pertinent English-language literature, which revealed only 26 previously reported oral LECs. Our case is only the fourth oral LEC originating from the surface epithelium and the first one to affect the gingiva.

Richter transformation in the oral and maxillofacial area: report of 2 cases and literature review.

Richter transformation (RT) is a term used to refer to the development of an aggressive lymphoma, usually of diffuse large B-cell lymphoma type, in a patient with a history of chronic lymphocytic leukemia. It may present with heterogeneous manifestations, including the occurrence of tumors at extranodal sites. To date, only 6 cases of RT involving the oral and maxillofacial region have been reported. Here, we present 2 rare cases of lymphoma initially affecting the maxilla and the lower gingiva, respectively, of female patients with chronic lymphocytic leukemia and review the English language literature about RT manifesting in the oral and maxillofacial tissues.

Localized juvenile spongiotic gingival hyperplasia: Microscopic variations and proposed change to nomenclature.

OBJECTIVES: Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a recently described entity with distinct manifestations. Herein we report a comprehensive histopathologic study of 21 lesions and a literature review. Additionally, we propose a new term that we consider more appropriate. STUDY DESIGN: LJSGH cases were retrieved and their clinicopathologic characteristics were assessed. A review of all pertinent literature was also conducted. RESULTS: Eighteen patients with LJSGH (21 biopsied lesions) were identified. Microscopically, surface morphology was classified into exophytic/papillary, flat, and micropapillary (8, 7, and 6 lesions, respectively). Cases with parakeratinization (n = 9), no prominent spongiosis (n = 5), or epithelial atrophy (n = 4) were recorded. Increased vascularity, mixed inflammation with exocytosis, and cytokeratin-19 positivity were uniformly observed. Less frequent findings included pseudoepitheliomatous hyperplasia (n = 8), bacterial colonies (n = 5), acantholysis (n = 3), and dystrophic calcifications (n = 2). The literature review disclosed 201 patients with a mean age of 14.8 years (range, 3-72; 13.6% affecting adults), similar sex distribution (103:98, female:male), and predominance of the anterior maxilla (≈ 80%). Eighteen cases were multifocal (≈ 10%). CONCLUSIONS: Our data suggest that the terminology could be modified, because LJSGH may be multifocal, affect older individuals, or exhibit epithelial atrophy, and the entity's odontogenic origin (as highlighted by the histopathologic and immunohistochemical findings) needs to be emphasized.