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JADA Specialty Scan - O & M Pathology
JADA Specialty Scan

Geographic tongue and IL36RN gene mutations

Geographic tongue (GT) is a benign inflammatory disorder of unknown etiology characterized by erythematous lesions secondary to desquamated filiform papillae and surrounded by white to yellow borders. Some cases of GT have been shown to be associated with generalized pustular psoriasis (GPP). To investigate molecular mechanisms of GT, the authors recruited 3 cohorts for genotyping of the interleukin 36 receptor antagonist gene, IL36RN, the causative gene of GPP. The study was published online November 29 in Human Genetics.

The first cohort was a Han Chinese family with GT alone. This 3-generation family consisted of 16 people, 6 of whom had GT and 1 had fissured tongue. All clinically affected family members were heterozygous for a c.115+6T>C(p.Arg10ArgfsX1) IL36RN variant. Three unaffected family members also carried this variant. None of the family members lacking this IL36RN variant had GT or fissured tongue.

The authors also recruited 48 patients with “sporadic” cases of GT alone and 168 randomly selected control participants. Sequencing revealed 3 variants of the IL36RN gene in 16 of these patients. The authors observed a highly significant association (odds ratio, 16.30; 95% confidence interval, 5.57 to 47.68) between the combined IL36RN genotypes and GT, suggesting that these IL36RN variants are risk factors for sporadic GT.

The third cohort consisted of 56 inpatients with GPP and 67 family members. Thirty-four of these patients (61%), all of whom also had GT, were identified as having IL36RN mutations. The other 22 inpatients, 13 of whom had GT, did not have IL36RN mutations. Of the 67 family members of the GPP probands, 42 had IL36RN mutations and 25 did not. Notably, 32 of the 67 family members (47.8%) were identified as having GT.

The study results show that some cases of GT were associated with autosomal-dominant IL36RN mutations, with an estimated penetrance of 70%. The authors propose that these cases “can be regarded as a localized manifestation of GPP.” Cases of GT lacking the IL36RN mutation were “associated with an imbalance in protein expression between IL-36Ra and IL-36γ in tongue tissue,” the authors wrote.

Read the original article.


Consulting Editor: Paul C. Edwards, MSc, DDS, FRCD(C)
Editor, American Academy of Oral and Maxillofacial Pathology
Professor, Department of Oral Pathology, Medicine and Radiology
School of Dentistry, Indiana University

Associate Consulting Editor: Kelly R. Magliocca, DDS, MPH
Assistant Professor of Oral and Maxillofacial Pathology
Department of Pathology and Laboratory Medicine
School of Medicine, Emory University

Oral mucous membrane pemphigoid and pemphigus vulgaris

Few studies have compared oral mucous membrane pemphigoid (MMP) with pemphigus vulgaris (PV). In a study published online January 13 in Oral Diseases, researchers analyzed the oral features, extraoral involvement, and treatment outcomes in patients with these uncommon chronic autoimmune diseases.

This retrospective, 2-center study comprised 26 patients with MMP and 31 patients with PV. The authors collected demographic data, including sex, concurrent medications, self-reported duration of symptoms before the initial visit, and previous treatments. Most patients (92%) with MMP were female compared with 65% of patients with PV. The median age of patients in both groups was in the fifth decade. At the time of the initial visit, 62% of those with MMP were receiving, or had received, topical corticosteroid treatment compared with only 19% of patients with PV. No patients with MMP and 35% of patients with PV were receiving, or had received, systemic corticosteroid treatment at the time of the initial visit.

The authors reported the presence of desquamative gingivitis (DG) in 84% of patients with MMP but in only 28% of those with PV. Furthermore, in 65% of patients with MMP, DG was the only manifestation of disease; by contrast, only 6% of patients with PV exhibited DG alone. At the initial visit, all patients with MMP exhibited oral involvement exclusively; at follow-up, only 1 had developed cutaneous lesions. Despite the absence of ocular involvement noted in the cohort of patients with MMP, all patients diagnosed with the disease were referred to an ophthalmologist for assessment and long-term follow-up. The authors emphasized that it “remains standard of care for patients with oral MMP to undergo routine ophthalmologic monitoring due to the potentially severe consequences that can lead to ocular scarring and blindness.”

Most patients with PV (84%) displayed symptoms at pharyngeal, nasal, cutaneous, vaginal, ocular, and anogenital sites at the initial visit; only 16% exhibited oral cavity involvement exclusively.

Of the 26 patients with MMP, 23 (88%) received topical corticosteroid therapy alone at the first visit, while the remaining 3 also received systemic therapy because of more widespread oral disease. At the first follow-up visit, control of disease activity was achieved in 85% of patients. Of the 31 patients with PV, 12 (39%) received topical corticosteroid therapy alone at the initial visit, and 19 (61%) received systemic therapy. Nevertheless, the authors noted that topical corticosteroid therapy alone is insufficient to control PV because it is a multisite systemic autoimmune condition that will progress in the absence of appropriate early systemic therapy. They stated that “early systemic treatment with corticosteroids, steroid-sparing agents (such as azathioprine, cyclophosphamide, and mycophenolate mofetil) and biologic therapies (such as rituximab and intravenous immunoglobulin) is important in achieving sustained remission and preventing disease progression.”

The self-reported median duration of symptoms before the first visit was 10 months for patients with MMP versus 6 months for those with PV. The authors explain that “patients with PV have a more severe disease course and may have significant extraoral involvement, prompting them to present earlier to their clinicians.” On the other hand, patients with MMP may receive conventional treatment for “gingivitis” for some time before being referred for consultation, or they may not seek help until symptoms worsen.

The authors conclude that oral MMP manifests primarily as DG and is “highly amenable to topical therapy,” whereas PV is a systemic mucocutaneous disease involving extensive nongingival oral lesions that “almost always requires systemic therapy.”

Read the original article.


Mark your calendar for 2017 meeting

Join AAOMP for our Annual Meeting April 28-May 3, 2017 at Gurney’s Resort and Marina (formerly the Hyatt Regency Newport) in Newport, RI. Visit for more details.


Population-based screening for early detection of oral premalignancy

The authors evaluated the effectiveness of a population-based screening program for the early detection of oral premalignancy (OPM) among high-risk people in Taiwan. Between 2004 and 2009, more than 4 million people from the National Nutrition and Health Survey who were 18 years and older and smoked cigarettes, chewed betel quid, or both were targeted to participate in this biennial oral screening program. The study was published online January 5 in Cancer.

Information on demographic characteristics and smoking and betel quid chewing habits was collected via face-to-face interviews in the communities and hospitals. The authors excluded people who were diagnosed with oral cancer before being invited to participate in the study. OPM was defined as oral leukoplakia, erythroleukoplakia, erythroplakia, oral submucous fibrosis, and verrucous hyperplasia. Oral cancer staging was based on the American Joint Committee on Cancer staging system.

Trained dentists and physicians performed the oral visual inspections. Participants with positive screening results were referred to specialists for a confirmatory pathologic examination. Those whose screening results were negative were invited to the next screening 2 years later. During the screening intervals, researchers followed up participants to identify cancers via linkage with the National Cancer Registry. They also monitored nonparticipants who were diagnosed with OPM or oral cancer.

Of the 4,234,393 eligible people, 2,334,299 (55.1%) participated in the first screening, 484,247 (11.4%) underwent at least 2 screenings, and 114,856 (2.7%) underwent at least 3 screenings. During the entire study period, 8,033 oral cancers were diagnosed among people who underwent screening. Of the 1,900,094 nonparticipants, 24,184 were diagnosed with oral cancer. Interestingly, the detection rates of OPM and oral cancer were slightly but statistically significantly higher for patients inspected by dentists compared with physicians.

Information about tumor stage was available for 87.4% of the 8,033 screened people in whom cancer was detected; 41 had carcinoma in situ, 1,837 had stage I disease, 1,388 had stage II disease, 879 had stage III disease, and 2,878 had stage IV disease. The study results show that the screened group had a higher proportion of early-stage oral cancer than the nonscreened group (46.5% versus 39.6%; P < .01). In addition, the overall incidence rate of oral cancer in the group that underwent screening was statistically significantly lower than that in the group that did not undergo screening. The authors explain that the “reduction in oral cancer incidence is mainly because malignant transformation is prevented through the early detection and treatment of OPMs that are detected by oral visual inspection.”

The authors note that the relative risk of dying from oral cancer was 0.53 as a result of screening compared with the expected risk of dying from oral cancer in the absence of screening. After adjusting for self-selection bias, the corresponding relative risk was 0.74.

The authors point to a 26% reduction in oral cancer mortality in participants compared with nonparticipants. They explain that this finding is consistent with a survival benefit because mortality reduction is a function of reductions in oral cancer incidence and improved survival. The research also shows a 21% reduction in advanced oral cancer (stage III or IV disease) among those who underwent screening compared with those who did not.

This study also provided information about subtypes of OPM, which is an “important part of evaluating the impact of reducing oral cancer if oral malignant transformation through OPM is to be arrested,” the authors wrote. They conclude that the study’s evidence-based findings support oral cancer screening among high-risk people in areas with a high incidence of oral cancer.

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Smokeless tobacco use and head and neck cancer

The prevalence of smokeless tobacco use in the United States was 2.7% in 2010. Previous epidemiologic studies on smokeless tobacco and head and neck cancer (HNC) in the United States have produced mixed results. The authors note that “given the relatively small sample sizes of previous studies, estimates for ever use of smokeless tobacco products were often imprecise, and frequency and duration of use, as well as exclusive use, of smokeless tobacco products were largely unexplored.” They also observed that some studies had limited information on other risk factors, particularly cigarette smoking. To address this concern, researchers used pooled data from case-control studies in the International Head and Neck Cancer Epidemiology Consortium to analyze associations between use of snuff (ground tobacco leaves that are inhaled into the nasal cavity or placed into the mouth) and chewing tobacco and HNC. The study was published online October 15 in American Journal of Epidemiology.

The study comprised 6,772 cases and 8,375 controls from 11 studies conducted across the United States between 1981 and 2006. Most studies were hospital based, with participants matched by age and sex. One-half of case and control participants were between the ages of 50 and 65 years, more than 80% were non-Hispanic white, and more than two-thirds were male.

The authors estimated odds ratios (ORs) and 95% confidence intervals (CIs) for ever use, frequency of use, and duration of use of snuff and chewing tobacco for never and ever cigarette smokers. They used hierarchical logistic regression, with study centers as a random effect.

The study results show a strong association between ever use of snuff and HNC—particularly oral cavity cancers—among ever snuff users who never smoked cigarettes (OR, 1.71; 95% CI, 1.08 to 2.70). Use of chewing tobacco was only weakly associated with HNC among participants who never smoked cigarettes (OR,1.20; 95% CI, 0.81 to 1.77), but analyses restricted to cancers of the oral cavity showed a stronger association. The authors observed few or no positive associations between use of chewing tobacco or snuff and HNC among participants who ever smoked cigarettes.

The large number of case and control participants in this study enabled the authors to estimate associations between smokeless tobacco and HNC among never smokers with “reasonable precision.” The authors note that “additional large studies [that] examine smokeless tobacco use separately from joint smoking and smokeless tobacco use are needed to more precisely estimate associations with HNC.” In addition, studies composed of more minority and international populations would contribute to the literature, as would those that focus on groups associated with high use of smokeless tobacco, such as workers in the construction and mining industries.

Read the original article.

2017 AAOMP Annual Meeting

Join the AAOMP at our Annual Meeting, April 28-May 3, 2017 in Newport, RI.

Earn CE credits by attending our AAOMP Seminar, chaired by Ellen Eisenberg, DMD with panelists Kitrina G. Cordell, DDS, MS, Robert D. Kelsch, DMD, Easwar Natarajan, BDS, DMSc, Carla R. Penner, DDS and Renee Reich, DDS.

Also at the meeting is our AAOMP Symposium – Panel Discussion on “Starting and Maintaining a Successful Career in Oral & Maxillofacial Pathology” Brent T. Accurso, DDS, MPH (Moderator) John E. Kacher, DDS Audrey Boros, MSc, DDS, and Sarah G. Fitzpatrick, DDS Donald M. Cohen, DMD, MS, MBA, and Christine Goergen, HTL(ASCP)CM  Paul D. Freedman, DDS Douglas D. Damm, DDS

Other CE programs include: “Extra-nodal Lymphomas of the Head and Neck” with Judith Ferry, MD, “Newly described entities in Head and Neck Pathology” with Justin Bishop, MD, Clinical Oral Pathology/Oral Medicine Update with Karen Baker, MS, Pharm. and the Founders Memorial Seminar – “Whose WHO in Head and Neck Pathology” with Lester Thompson, MD. For up to date information, click here.

Give Your Patients the Facts About Mouth and Throat Cancer

With roughly 45,000 new cases of mouth and throat cancer diagnosed each year, it’s imperative that your patients know the signs, the risks and how you can help them. The patient education brochure, Get the Facts About Mouth and Throat Cancer helps you convey the importance of changing risky behavior. It also encourages your patients to consult with you whenever they have a symptom. 

The 6-panel brochure includes pictures of cancer on the tongue, cancer on the lip, and leukoplakia.  A sample can be viewed here. To order, call 1-800-947-4746 or go to  Readers who use the code 17407E before March 31 can save 15 percent on all ADA Catalog products. 


Mark your calendar for 2017 meeting

Join AAOMP for our Annual Meeting April 28-May 3, 2017 at Gurney’s Resort and Marina (formerly the Hyatt Regency Newport) in Newport, RI. Visit for more details.


What is Specialty Scan?

This is one in a series of quarterly newsletters updating dentists on selected specialties in dentistry. Information presented is aggregated and summarized from previously published materials, each item attributed to its publication of origin. This issue of JADA Specialty Scan focuses on oral pathology, the first in the series on this topic for 2017. Other Specialty Scan issues are devoted to endodontics, oral and maxillofacial radiology, orthodontics, pediatric dentistry, periodontics and prosthodontics. The ADA has engaged the specialty organizations in these areas as well as its own Science Institute and Division of Legal Affairs to assist with these newsletters. We welcome feedback on this and all Specialty Scan issues.

Editorial and Advertising Policies

Any statements of opinion or fact are those of the authors and do not necessarily reflect the views of the American Dental Association. Neither the ADA nor any of its subsidiaries have any financial interest in any products mentioned in this publication. Any reference to a product or service, whether in advertisements or otherwise, is not intended as an endorsement or as approval by the ADA or any of its affiliated organizations unless accompanied by an authorized statement that such approval or endorsement has been granted.

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