Management of oral herpes simplex virus infections: The problem of resistance. A narrative review.

Herpes Simplex Virus (HSV) type 1 (HSV-1) and type 2 (HSV-2) are among the most common human viral pathogens, affecting several billion people worldwide. Although in healthy patients clinical signs and symptoms of HSV infection are usually mild and self-limiting, HSV-infections in immunocompromised patients are frequently more aggressive, persistent, and even life-threatening. Acyclovir and its derivatives are the gold standard antiviral drugs for the prevention and treatment of HSV infections. Although the development of acyclovir resistance is a rather uncommon condition, it may be associated with serious complications, especially in immunocompromised patients. In this review, we aim to address the problem of drug resistant HSV infection and discuss the available alternative therapeutic interventions. All relative studies concerning alternative treatment modalities of acyclovir resistant HSV infection published in PubMed between 1989 to 2022 were reviewed. Long-term treatment and prophylaxis with antiviral agents predisposes to drug resistance, especially in immunocompromised patients. Cidofovir and foscarnet could serve as alternative treatments in these cases. Although rare, acyclovir resistance may be associated with severe complications. Hopefully, in the future, novel antiviral drugs and vaccines will be available in order to avoid the existing drug resistance.

Co-existence of Congenital Epidermoid Cyst and Ranula in a Newborn. Report of a Unique Case.

Background: Congenital cystic swellings involving the floor of the mouth include various lesions such as developmental cysts (e.g., dermoid and epidermoid cysts), ranulas, vascular malformations etc. However, coexistence of such conditions, possibly with a cause-and-effect- relationship, is rare. The purpose of this case report is to present a rare case of a congenital epidermoid cyst associated with a mucous retention cyst in a newborn. Methods: A 6-month-old female infant was referred to an Oral Medicine Clinic in Athens, Greece on October 2019 for evaluation of a swelling at the floor of the mouth, first noticed by her paediatrician just after birth. Clinically, a yellowish "pearly" nodule in close association with the orifice of the left submandibular duct, posteriorly transitioning to a diffuse bluish cystic swelling of the left floor of the mouth was observed. With a provisional diagnosis of a dermoid cyst and/or ranula, a surgical excision was performed under general anaesthesia. Results: Histopathologically, a well-defined, keratin-filled, cystic cavity lined by orthokeratinized stratified squamous epithelium was observed in the anterior aspect while posteriorly and in close proximity, a dilated salivary duct lined by cylindrical, cuboidal or pseudostratified epithelium was noted. A final diagnosis of an epidermoid cyst intimately associated with a mucus retention cyst (ranula) of the submandibular duct was rendered. Conclusions: The coexistence of two cystic lesions in the floor of the mouth with features of epidermoid and mucous retention cyst, respectively, is rare and its pathogenesis intriguing, especially in a newborn.

Cheilitis Glandularis: A clinicopathologic study with emphasis on etiopathogenesis.

OBJECTIVES: Cheilitis Glandularis (CG) is an uncommon entity of obscure etiology. A cases series is presented with emphasis on etiopathogenesis. MATERIALS AND METHODS: Fourteen CG cases were analyzed according to their demographic and clinicopathologic characteristics. RESULTS: The mean age of the patients with CG was 68.1 years, while a male-to-female ratio of 1.8:1 was observed. One or more potential causative factors were identified for each patient, including long-term smoking (9 cases), xerostomia (4 cases), cosmetic filler injections (2 cases), and actinic cheilitis (1 case). The lesions were located on the lips, buccal mucosa, or both in 7, 2, and 5 cases, respectively. Multiple submucosal nodules with dilated ductal orifices and mucous or purulent discharge were observed in all cases. Histopathologically, ductal ectasia with metaplasia, intraductal mucin, and chronic or mixed inflammation were noted, as well as pools of hyaluronic acid in 2 cases with a history of cosmetic filler injections. CONCLUSIONS: CG etiopathogenesis is probably multifactorial. Reduced salivary flow rate and increased viscosity of saliva, potentially caused by long-term smoking, diabetes mellitus, and drug-induced xerostomia, may participate in the initial pathogenesis, while local irritants, for example, poor oral hygiene and local trauma, may further contribute to the development and aggravation of the condition.

Oral Side Effects in Patients with Metastatic Renal Cell Carcinoma Receiving the Antiangiogenic Agent Pazopanib-Report of Three Cases.

Pazopanib is a potent multi-kinase inhibitor that hinders angiogenesis and blocks tumor growth. It has been approved for the treatment of metastatic renal cell carcinoma (mRCC) and advanced soft tissue sarcoma. There is emerging evidence that bleeding is a common adverse effect of pazopanib and other targeted therapies in patients with mRCC. In addition, jaw osteonecrosis related to pazopanib was recently described in the literature. We report three cases of patients with mRCC who developed adverse oral events related to pazopanib. The first patient, treated with pazopanib as monotherapy, presented with gingival bleeding and oral burning sensation. The other two patients receiving pazopanib as monotherapy and pazopanib followed by sunitinib, respectively, presented complaining about mandibular pain; a diagnosis of medication-related osteonecrosis of the jaw (MRONJ) was rendered in both cases. Gingival bleeding and MRONJ may develop as oral side effects of pazopanib use. The cases presented here aim to alert and inform health care professionals about the risk of adverse oral events in patients with mRCC receiving the antiangiogenic agent pazopanib.

Cytokine profiling in plasma distinguishes the histological inflammatory subtype of head and neck squamous cell carcinoma and a novel regulatory role of osteopontin.

Head and neck squamous cell carcinoma (HNSCC) can be classified according to the histological inflammatory subtype (HIS) into inflamed (HIS-INF) or immune excluded (HIS-IE). HIS-IE was previously associated with higher levels of soluble Semaphorin 4D (HsS4D) in plasma, and higher transcriptional levels of osteopontin (OPN) in the tumor tissue, compared to HIS-INF. The goal of the current study is to investigate whether the HIS inflammatory subtype can be distinguished by a differential cytokine panel in peripheral blood. Retrospectively collected five HIS-INF and five HIS-IE tumor tissue with paired plasma were included in the study. Five healthy donors (HD) and five autoimmune/chronic inflammatory conditions (AI/CI) were controls. The ELISA-Luminex™ system was used to detect 40 traditional cytokines in plasma. Human cytokine array (104 cytokines) was used for the conditioned medium (CM) of the HNSCC HN6 cell line. Semaphorin 4D (Sema4D) siRNA and recombinant human osteopontin (rh-OPN) were used to investigate the effect of OPN on Sema4D expression. The HIS-IE cytokine profile was higher than HIS-INF but comparable to AI/CI. HIS-INF had the lowest cytokine levels. HIS-IE was differentially higher in IP-10 and IL8 compared to HD, while HIS-INF was higher in IL-10. Sema4D inhibition in HN6 resulted in a decrease of OPN in the CM of HN6, and treatment with rh-OPN rescued Sema4D in HN6 cell lysate and associated CM. In conclusion, the current work demonstrates a novel association between the HIS subtypes and a differential pattern of cytokine expression in plasma. These findings can open new avenues for HNSCC patient stratification and hence provide better personalized treatment.

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.

Expression of BMP4 and FOXN1 in orthokeratinized odontogenic cyst compared to odontogenic keratocyst suggests an epidermal phenotype.

Odontogenic keratocysts (OKC) and orthokeratinized odontogenic cysts (OOC) are odontogenic cysts that share histological and immunohistochemical similarity with epidermal appendages and cutaneous cystic lesions despite exhibiting contrasting biological behavior. In epidermal appendages, BMP4 induces expression of FOXN1, which participates in terminal differentiation of keratinocytes and control of proliferation. We compared BMP4 and FOXN1 expression in OOC and OKC to investigate their role in the epithelial differentiation of these cysts. BMP4 and FOXN1 expression was assessed using immunohistochemistry in 20 primary sporadic OKC and compared to 16 OOC. BMP4 epithelial expression was detected in 81.25% OOC compared to 35% in OKC, while its expression in connective tissue was observed in 65% OKC and 75% OOC. FOXN1 was detected in 75% OOC vs. 30% OKC. The "triple positive" phenotype, i.e., BMP4 epithelial and connective tissue positivity and FOXN1 epithelial positivity, was seen in 56.25% OOC compared to 10% OKC. The greater expression of BMP4 and FOXN1 in OOC suggests greater activation of this pathway in OOC, which suggests a role in its more mature epithelium; it also resembles an epidermal phenotype.

Base of tongue metastasis of cutaneous malignant melanoma with rhabdoid and neuroendocrine features: Report of a rare case and review of the literature.

Metastatic malignant melanoma (MM) represents a highly aggressive cancer associated with overall poor prognosis. Various anatomic sites can be affected, including the oral cavity and the oropharynx. It may mimic other entities by assuming a variety of clinical appearances and exhibiting a plethora of microscopic variations. Herein, we present a case of a 63-year-old male with a MM metastasizing to the base of tongue, which developed 5 years after the original diagnosis and treatment of cutaneous MM of the chest and heralded its relapse; subsequently, neurological symptoms developed as a result of metastasis to the brain. Diagnostic challenges were encountered, as the tongue lesion clinically masqueraded as a pedunculated reactive lesion and microscopically displayed unusual rhabdoid and neuroendocrine features. Tumor cells expressed S-100, HMB-45, Melan-A, and SOX-10, while most cells with rhabdoid morphology were also positive for myogenin and Myo-D1. Chromogranin and synaptophysin positivity was further noticed in a subset of cells, suggestive of focal neuroendocrine differentiation. Molecular investigation revealed mutations for the BRAF V600E gene. Divergent differentiation of tumor cells may cause diagnostic pitfalls necessitating thorough immunohistochemical analysis. The presence of rhabdoid features and neuroendocrine differentiation are very uncommon, while their co-existence is extremely rare. Better characterization of such microscopic variations in MMs with evaluation of their potential biologic significance is warranted.

Scleroderma-specific autoantibodies: Should they be included in the diagnostic work-up for Sjögren's syndrome?

OBJECTIVES: Sicca complaints are a frequent reason for rheumatologic consultation. Testing for specific antibodies against Ro/SSA and La/SSB antigens and minor salivary gland (MSG) biopsy are among the main tools implemented in the diagnostic work-up. Anticentromere antibodies and sicca manifestations are frequently detected in Sjögren's syndrome (SS) and systemic sclerosis (SSc), respectively. Herein, we aimed to determine the frequency and clinical associations of a wide spectrum of scleroderma (SSc)-specific autoantibodies in consecutive patients referred for evaluation of possible SS. METHODS: Demographic, clinico-pathological, and laboratory data were recorded in 216 consecutive patients with sicca complaints. All study participants were tested for SSc-specific autoantibodies (against CENP, PM/Scl, Scl-70, Ku, NOR90, RP11, RP155, fibrillarin, PDGFR, and Th/To) using a commercially available immunoblot kit. According to band intensity, the identified autoantibodies were further classified in those with strong and medium titers. RESULTS: SSc-specific autoantibodies were detected in 41.7% (90/216) patients evaluated (19% at strong, 22.7% at medium titers) without significant differences between anti-Ro/SSA positive and negative groups. At strong titers was significantly higher in patients with MSG biopsies fulfilling SS histopathological criteria (30% vs 12.5%, p = 0.009). This association remained significant after adjustment for antibodies against Ro/SSA and La/SSB autoantigens [OR 95% (CI): 4.1 (1.5-10.6)]. CONCLUSION: SSc-specific autoantibodies are frequently detected among patients presenting with sicca complaints and at strong but not medium titers are independently associated with MSG biopsy positivity. Taken together, these data imply a useful role of SSc antibody testing in the diagnostic work-up and possibly in the classification criteria for SS.

Acquired Compound Melanocytic Nevus on the Palate of a Child: Report of a Case.

Background: Oral melanocytic nevi are relatively rare in comparison to their cutaneous counterparts. The aim of this manuscript is to present a case of acquired compound oral melanocytic nevi on the hard palatal mucosa of a child. Methods: A 5-year-old female girl was referred for evaluation of a pigmented lesion on the hard palate. The lesion was asymptomatic and present for approximately 2 months. Oral clinical examination revealed a well-circumscribed brownish macule on the hard palatal mucosa, adjacent to the left first primary upper molar. Considering the recent onset of the lesion, biopsy was recommended, but the patient returned 3 years later, when increase in size with slight asymmetry and colour variation were noticed. An excisional biopsy was performed. Results: Microscopic examination revealed nevus cells randomly distributed along the basal cell layer and organized into nests along the junctional area and within the papillary layer of lamina propria, while immunohistochemical evaluation showed positivity of nevus cells for SOX-10 and Melan-A. A final diagnosis of compound melanocytic nevi was rendered, and the patient was advised to attend regular follow-up appointments. Conclusions: Although oral melanocytic nevi are rare in childhood, their potential development should not be overlooked. Acquired oral melanocytic nevi need to be differentiated from several other common (e.g. amalgam tattoo) and uncommon (e.g. melanoma) oral pigmented lesions, as well as from the more rare congenital oral melanocytic nevi. Oral melanocytic nevi with junctional activity (i.e. junctional, compound subtypes) appear to be more common in children, possibly reflecting an earlier developmental stage.

A randomized clinical trial of topical dexamethasone vs. cyclosporine treatment for oral lichen planus

Background: Oral lichen planus (OLP) is a common, frequently symptomatic, immune-mediated disease. Various treatments have been used for symptomatic OLP, including corticosteroids and immunosuppressants administered topically or systemically. The aim of this study was to compare the effectiveness of topical dexamethasone vs. topical cyclosporine in treatment of symptomatic OLP. Material and Methods: Thirty-two patients with biopsy-proven symptomatic OLP were randomly assigned to two therapeutic groups: dexamethasone 2mg/5ml or cyclosporine 100mg/ml, both administered topically in a swish and spit method three times a day for 4 weeks. The patients were followed up for a total of 6 months. Assessed parameters included clinical scoring (according to Thongprasom’s scale, 0-5), pain (VAS scale, 0-10), dysphagia and speech difficulties (none, mild or severe). Possible side effects, including fungal overgrowth, were also recorded. Results: At the end of the 4-week treatment period, both dexamethasone and cyclosporine showed a statistically significant improvement in clinical scoring (p<0.025 and p=0.034, respectively), which was better with dexamethasone (p=0.001). In addition, both dexamethasone and cyclosporine induced statistical significant improvement in pain and dysphagia (and speech difficulties for dexamethasone), without significant differences between the two groups. Regarding side effects, patients in the dexamethasone group developed candidiasis more frequently compared to cyclosporine (p=0.031). At the end of the 6-month follow-up period, the difference in response between the two groups was not statistically significant. Interestingly, a trend for further improvement compared with the end of the 4-week treatment period was noticed only for patients treated with cyclosporine. Conclusions: Despite the small number of enrolled patients, topical cyclosporine treatment induces a significant clinical improvement in symptomatic OLP patients, which, compared to topical dexamethasone, appears to be less pronounced during initial administration, but capable to induce further improvement after discontinuation with a satisfactory long-term remission in the absence of significant side effects. This study may contribute to a better understanding of the differences in effectiveness of OLP topical treatments and guide future larger scale clinical trials.(AU)

Aplasia of the Major and Minor Salivary Glands: Report of a Rare Case.

Background: Aplasia of the salivary glands, either partial or involving all the major and possibly the minor salivary glands, is a very rare cause of hyposalivation. The aim of this case report is to present a case of aplasia of the major and minor salivary glands and discuss the relevant literature. Methods: A 23-year-old woman, with a non-contributory medical and family history was referred due to rampant caries, that could not be attributed to any obvious aetiology. No sicca symptoms, previous parotid gland swelling or general symptoms were reported. Clinically, oral mucosa dryness and extended dental erosions and caries were observed, while the orifices of the excretory ducts of the parotid and submandibular salivary glands were not evident. Unstimulated and stimulated saliva flow rates were severely diminished, while a diagnostic biopsy of the lower lip revealed absence of minor salivary glands. Detailed hematologic and immunological investigations to exclude systemic disorders were also within normal limits. Ultrasound and magnetic resonance imaging revealed the absence of all major salivary glands, confirming the clinical diagnosis of congenital aplasia of the salivary glands. Results: Oral hygiene instructions and dietary advice were given while dental products with fluoride and saliva substitutes were administered and appropriate dental treatment was implemented. Regular dental follow-up was also advised. Conclusions: Timely diagnosis of aplasia of the salivary glands is important, considering the detrimental effects of the absence of saliva on oral health. Management consists of the use of saliva substitutes, nutritional adaptation, maintenance of oral health and regular dental follow-ups.

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.

Interferon (IFN)-stimulated gene 15: A novel biomarker for lymphoma development in Sjögren's syndrome.

OBJECTIVE: We investigated whether interferon (IFN) induced genes could serve as biomarkers for the detection of lymphoma development among patients with Sjögren's syndrome (SS). METHODS: Total RNA was extracted from 98 labial minor salivary glands (LMSG) biopsies of SS patients [61 not complicated by lymphoma (SS-nL) and 37 complicated by Non-Hodgkin Lymphoma (NHL) (SS-L)] and 67 matched peripheral blood (PB) samples, as well as from 30 LMSG biopsies and 17 matched PB derived from sicca controls (SC). RNA sequencing was performed in LMSG biopsies of high and low risk SS patients for lymphoma development and SC. Expression analysis of type I (MX-1, IFIT-1, IFI44 and ISG-15) and type II IFN induced (CXCL9/MIG-1, GBP-1) genes was performed by real time PCR. RESULTS: ISG-15 transcript levels were significantly higher in SS-L patients compared to SS-nL patients in both LMSG tissues and PB specimens. Additionally, MIG-1 was found to display higher expression values in LMSG tissues, but not in PB derived from SS-L patients compared to the SS-nL group. A coordinate expression in PB/LMSG of type I IFN (ISG-15, MX-1 and IFI44), but not type II IFN induced genes was also observed. CONCLUSION: ISG-15 gene expression was able to distinguish SS-nL and SS-L at both periphery and tissue level and therefore could represent a novel biomarker for lymphoma development among SS patients. PB and LSMG seem to share a common transcriptional profile of type I IFN pathway.

Recurrence in Oral Premalignancy: Clinicopathologic and Immunohistochemical Analysis.

Oral leukoplakia (OL) has a propensity for recurrence and malignant transformation (MT). Herein, we evaluate sociodemographic, clinical, microscopic and immunohistochemical parameters as predictive factors for OL recurrence, also comparing primary lesions (PLs) with recurrences. Thirty-three patients with OL, completely removed either by excisional biopsy or by laser ablation following incisional biopsy, were studied. Selected molecules associated with the STAT3 oncogenic pathway, including pSTAT3, Bcl-xL, survivin, cyclin D1 and Ki-67, were further analyzed. A total of 135 OL lesions, including 97 PLs and 38 recurrences, were included. Out of 97 PLs, 31 recurred at least once and none of them underwent MT, during a mean follow-up time of 48.3 months. There was no statistically significant difference among the various parameters in recurrent vs. non-recurrent PLs, although recurrence was most frequent in non-homogeneous lesions (p = 0.087) and dysplastic lesions recurred at a higher percentage compared to hyperplastic lesions (34.5% vs. 15.4%). Lower levels of Bcl-xL and survivin were identified as significant risk factors for OL recurrence. Recurrences, although smaller and more frequently homogeneous and non-dysplastic compared to their corresponding PLs, exhibited increased immunohistochemical expression of oncogenic molecules, especially pSTAT3 and Bcl-xL. Our results suggest that parameters associated with recurrence may differ from those that affect the risk of progression to malignancy and support OL management protocols favoring excision and close monitoring of all lesions.

Tongue Atrophy in Sjögren Syndrome Patients with Mucosa-associated Lymphoid Tissue Lymphoma: Autoimmune Epithelitis beyond the Epithelial Cells of Salivary Glands?

OBJECTIVE: Primary Sjögren syndrome (pSS), an autoimmune epithelitis, bears the risk of evolving to non-Hodgkin lymphoma and most frequently to the mucosa-associated lymphoid tissue (MALT) subtype. Based on the observation that pSS patients with MALT present a more atrophic and more intensely fissured tongue, we aimed to semiquantify severity of tongue atrophy and clinically assess lingual appearance in pSS patients with and without MALT, and investigate whether tongue atrophy and fissured appearance could serve as clinical indicators/signs of MALT. METHODS: A blinded complete oral examination was performed in pSS patients with and without MALT. Tongue atrophy was scored using a semiquantified atrophy score. Clinical and laboratory variables were recorded for all patients. RESULTS: After excluding pSS patients with oral candidiasis, iron deficiency, and megaloblastic anemia, 19 pSS patients with salivary MALT were matched 1:3 for age, sex, and disease duration with 57 pSS patients without MALT. The pSS-MALT patients had increased prevalence of salivary gland enlargement, lymphadenopathy, monoclonal gammopathy, rheumatoid factor positivity, higher focus and Tarpley scores in the minor salivary gland biopsy, and hyposalivation, compared to the pSS non-MALT patients. A significantly higher prevalence of tongue atrophy (68% vs 30%, p = 0.006) and fissured tongue (89% vs 33%, p < 0.001) was observed in the former group. Multivariate analysis showed that fissured tongue appearance, hyposalivation, and lymphadenopathy associate independently with salivary MALT in pSS. CONCLUSION: These results suggest that pSS patients with lymphoid malignancy exhibit a more atrophic and more fissured tongue. This particular clinical tongue appearance can serve as an additional clinical sign for salivary MALT lymphoma in pSS patients.

Oral foreign body granuloma to soft tissue fillers. Report of two cases and review of the literature.

The increasing demand for cosmetic procedures in the orofacial area nowadays, results in a growing number of complications attributable to soft tissue fillers, including the development of foreign body granuloma. The purpose of this study is to present two additional cases of oral foreign body granulomas caused by liquid silicone and hyaluronic acid respectively and review the pertinent literature regarding the demographics, the clinical appearance, the histopathology and the treatment of these lesions. Key words:Oral foreign body granuloma, hyaluronic acid, silicone, soft tissue filler.

Ductal cells of minor salivary glands in Sjögren's syndrome express LINE-1 ORF2p and APOBEC3B.

BACKGROUND: Type I interferon activation is a hallmark event in Sjögren's syndrome. L1 retroelements stimulate plasmacytoid dendritic cells, activating the type I interferons, and are regulated by various mechanisms, including the APOBEC3 deaminases. As L1s are potential trigger factors in autoimmunity, we aimed to investigate the immunohistochemical localization of L1 ORF2p and its inhibitor APOBEC3B protein in minor salivary glands of Sjögren's syndrome patients. METHODS: Twenty minor salivary gland-tissue samples from 20 Sjögren's syndrome patients, classified according to Tarpley's histological criteria, and 10 controls were evaluated for L1 ORF2p and APOBEC3B expression via immunohistochemistry. RESULTS: L1 ORF2p was expressed in 17/20 SS patients and all controls. APOBEC3B expression was observed in 15/20 Sjögren's syndrome patients, 5/5 chronic sialadenitis, and 3/5 normal minor salivary glands. Both antibodies stained the cytoplasm of the ductal epithelial cells. Negative staining was observed in the acinar cells. L1 ORF2p-positive immunostaining was significantly lower in Tarpley IV Sjögren's syndrome patients than controls (P = .039), and APOBEC3B-positive staining was significantly lower in Tarpley I compared to Tarpley II Sjögren's syndrome patients (P = .008) and controls (P = .035). CONCLUSIONS: L1 ORF2p and APOBEC3B are expressed in the ductal epithelial cells of minor salivary glands that are among the key targets in Sjögren's syndrome. L1 ORF2p expression may promote the L1 ability to act as an intrinsic antigen in Sjögren's syndrome. The potential future use of L1 ORF2-reverse transcriptase inhibitors in autoimmunity supports further investigation of L1 epigenetic regulation by APOBEC3 enzymes.

MALT Lymphoma of Minor Salivary Glands in a Sjögren's Syndrome Patient: a Case Report and Review of Literature.

BACKGROUND: Sjögren's syndrome is a chronic systemic disease, characterized by lymphocytic infiltration and destruction mainly of the salivary and lacrimal glands, resulting in xerostomia and xeropthalmia. Sjögren's syndrome patients have a 44-fold excess risk for the development of non-Hodgkin's lymphoma particularly mucosa-associated lymphoid tissue (MALT) lymphoma, prevalently affecting the major salivary glands. In this report, a rare case of MALT lymphoma of minor salivary glands in a patient with Sjögren's syndrome is described. A review of the published cases of MALT lymphoma located in the minor salivary glands of patients with Sjögren's syndrome is provided. METHODS: In a 64-year-old female patient previously diagnosed with Sjögren's syndrome, an asymptomatic soft tissue mass at the palate was noticed, exhibiting rapid enlargement within one month. With a main differential diagnosis of salivary gland neoplasm or lymphoproliferative lesion, a partial biopsy was performed accompanied by proper immunohistochemical analysis. RESULTS: A final diagnosis of MALT lymphoma was rendered and the patient was referred for further multidisciplinary evaluation. Gastric endoscopy and biopsy revealed a Helicobacter pylori-negative gastric MALT lymphoma, while spleen involvement and bone marrow infiltration were also identified. Patient was classified as having stage IV disseminated disease and a standard chemotherapy protocol was administered; the treatment was well tolerated and resulted in complete remission. CONCLUSIONS: This case emphasizes the need for close monitoring of patients with Sjögren's syndrome by oral medicine specialists, which, besides ensuring proper management of xerostomia and its sequelae, may also lead to early recognition of lymphoma development.

Localized Juvenile Spongiotic Gingival Hyperplasia: Report of Two Cases.

OBJECTIVE: Localized juvenile spongiotic gingival hyperplasia (LJSGH) is a painless gingival swelling that histologically exhibits hyperplasia of the non-keratinized stratified squamous epithelium, intercellular edema and spongiosis of the spinus layer, and exocytosis of inflammatory cells. LJSGH pathogenesis remains to be elucidated, while a possible origin from the gingival sulcus epithelium is nowadays proposed. STUDY DESIGN: We report two cases of LJSGH with immunohistochemical evaluation of cytokeratins (CKs) 18 and 19. RESULTS: Both cases concerned 12-year-old boys, who presented with a well-circumscribed bright red pedunculated papillary swelling on the marginal gingiva of the left maxillary lateral incisor. With the provisional diagnosis of LJSGH, the lesions were excised under local anesthesia and histological examination supported the final diagnosis of LJSGH. In both cases, the lesional epithelium showed intense and mild positivity for CK19 and CK18, respectively, while the adjacent normal gingival epithelium expressed CK19, but not CK18, only in the basal cell layer. The postoperative course was uneventful in both patients and no recurrence has been reported. CONCLUSION: LJSGH is a recently introduced entity that is worth attention in the clinical pediatric dentistry. Clinical and histological examination is required for the final diagnosis, while immunohistochemistry has shed light to LJSGH pathogenesis.