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JADA Specialty Scan - O & M Pathology
O & M PathologyJADA Specialty Scan

The relationship between oral lichen planus and thyroid disease

Oral lichen planus (OLP) is an autoimmune mucocutaneous disease with a female predilection. Although the etiology is unclear, several researchers have observed an association between OLP and thyroid disease. In this systematic review and meta-analysis, researchers examined the relationship between OLP and thyroid disease. The results were published online November 9, 2017, in Frontiers in Endocrinology.

Inclusion criteria were any type of clinical study that explored the relationship between OLP and thyroid disease, as well as studies in which patients had received a clinical diagnosis of OLP. The presence of thyroid disease was the exposure of interest. The researchers placed no restrictions on age, sex, race, or country.

Two of the authors independently searched several databases for English- and Chinese-language studies that met the inclusion criteria. They also conducted a manual search for studies published through August 2016. Of the 830 articles identified in the initial search, 765 were excluded because they were duplicates, contained irrelevant information, or did not meet the inclusion criteria. Of the remaining studies, all but 8 were subsequently excluded for a variety of reasons. Four of the 8 studies included a control group; thus, these case-control studies—with a total of 1,846 participants—were included in the final meta-analysis. The researchers retained the other 4 studies for the literature review.

The odds ratio (OR) for the association between OLP and thyroid disease ranged from 1.71 (95% confidence interval [CI], 0.98 to 2.99) to 4.16 (95% CI, 2.38 to 7.29), indicating a statistically significant difference in the prevalence of thyroid disease between patients with OLP and control participants. The pooled OR was 2.63 (95% CI, 1.95 to 3.54).

The heterogeneity among the studies (I2) was 49%; thus, the researchers used a fixed-effects model for the meta-analysis. After a sensitivity analysis, heterogeneity was more satisfactory (I2 = 0%), and the combined OR among the 3 included studies was 2.10 (95% CI, 1.47 to 3.01).

Of the 8 studies in the literature review, 2 reported data pertaining to hypothyroidism. The researchers merged these data, which revealed a correlation between OLP and hypothyroidism (OR, 1.83; 95% CI, 1.16 to 2.89), with satisfactory heterogeneity (I2 = 0%).

This systematic review and meta-analysis showed a statistically significant correlation between OLP and thyroid disease. Thus, thyroid disease may be involved in the pathogenesis of OLP, or OLP may be a clinical manifestation of thyroid disease, the researchers concluded. Further studies are needed to elucidate the mechanism accounting for this association between OLP and thyroid disease. The authors suggest that patients with OLP undergo routine screening for thyroid disease.

Read the original article here.


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: Zoya Kurago, DDS, PhD
Associate Professor of Oral Biology, Oral Health and Diagnostic Sciences,
Graduate Studies, Pathology
Department of Oral Health and Diagnostic Sciences
Dental College of Georgia, Augusta University

Examining neurologic manifestations of primary Sjögren syndrome

Primary Sjögren syndrome (PSS) is an autoimmune inflammatory disease characterized by mononuclear lymphocytic infiltration of salivary and lacrimal glands in the setting of antinuclear antibodies. In this review article, published in the November 2017 issue of Rheumatic Disease Clinics of North America, researchers explore neurologic manifestations of the disease, underlying mechanisms, and treatment options.

Approximately 20% of patients with PSS experience neurologic manifestations. Patients may exhibit a variety of peripheral neuropathies, of which distal sensory and sensorimotor are the most common. Sensory neuropathies include painful nonataxic polyneuropathy, dorsal root ganglionitis, and trigeminal neuoropathy. Patients can experience severe pain in the proximal torso, extremities, or face, with small fiber neuropathy causing lancinating or burning pain. Sensorimotor polyneuropathy and mononeuritis multiplex are subtypes of sensorimotor neuropathies. Peripheral neuropathies associated less frequently with PSS include polyradiculoneuritis, autonomic neuropathy, and motor neuron disorder.

Clinicians can differentiate these peripheral neuropathies on the basis of the clinical presentation and results of electromyography and nerve-conduction studies, evoked potentials, and nerve and muscle biopsies.

The pathogenesis of peripheral neuropathies depends on the type of nerve involved, the authors wrote. In cases of sensory ganglioneuronopathy, pathology consists of the loss of neuronal cell bodies and lymphocytic infiltration. Similarly, ganglionitis is caused by lymphocytic infiltration into the dorsal root ganglia, with or without accompanying vasculitis. In other peripheral neuropathies, such as mononeuritis multiplex, vasculitis has been implicated as the primary mechanism. The authors cited a study involving 33 patients with PSS; sural nerve biopsies in 11 of these patients revealed perivascular inflammatory infiltrates and other vessel abnormalities, which were diagnostic in 2 cases and strongly suggestive of necrotizing vasculitis in 6 cases.

Patients with PSS may exhibit central nervous system (CNS) involvement. Clinical manifestations are varied and encompass focal central lesions, conditions that mimic multiple sclerosis, subacute encephalitis, aseptic meningitis, cerebellar syndromes causing ataxia, movement disorders affecting the basal ganglia producing chorea, neuromyelitis optica, and problems with memory, cognition, and depression. CNS involvement frequently precedes PSS diagnosis and may manifest as recurrent, multifocal episodes separated by lengthy, disease-free periods resulting in “insidious progressive neurologic deficits.” As with peripheral neuropathies, estimates vary widely regarding the frequency of CNS involvement in PSS.

Immunologically mediated small vessel vasculopathy seems to be the most common underlying mechanism in the pathogenesis of CNS involvement in PSS. Less common is a true small vessel vasculitis. The authors cited several studies to support the hypothesis of immunologically mediated vasculopathy and vasculitis being the drivers of CNS involvement in PSS.

Patients with clinically significant neurologic manifestations of PSS may need to undergo aggressive therapy with glucocorticoids and immunosuppressive agents. However, no randomized controlled trials involving intravenous (IV) immunoglobulin (Ig), immunosuppressive medications, or both have been conducted in patients with PSS and neuropathies or CNS disease. Furthermore, the heterogeneity of neurologic manifestations in PSS complicates treatment, which should be directed toward the underlying neuropathologic mechanism.

Symptomatic treatment of neuropathies often starts with gabapentin, the authors wrote. Intravenous Ig may be beneficial for those with peripheral motor or sensory neuropathies and peripheral demyelinating disorders that do not respond to glucocorticoids or other immunosuppressive agents.

Fludrocortisone acetate or midodrine is a treatment option for patients with autonomic neuropathy. The treatment approach for CNS manifestations of PSS depends on the underlying pathology, which may include vasculopathy, vasculitis, or demyelination. Intravenous Ig, glucocorticoids, cyclophosphamide, rituximab, azathioprine, and methotrexate have been used to treat CNS manifestations, with limited success, the authors concluded.

Read the original article here.


Mark your calendar for the 2018 Joint AAOMP and IAOP meeting
Join AAOMP and the IAOP for our Joint Meeting June 22-June 28, 2018 at the Westin Bayshore Hotel in Vancouver, BC, Canada. Visit for more details.


Risk factors for malignant transformation of oral potentially malignant disorders

Oral potentially malignant disorders (OPMDs), also referred to as potentially preneoplastic oral epithelial lesions, are lesions of the surface epithelium of the oral cavity associated with an increased risk of progressing to malignancy. This risk varies according to a range of patient- or lesion-related factors. In this review article, researchers examine risk factors for malignant transformation of leukoplakias and other OPMDs and provide an algorithm to aid in risk assessment. This review was published online December 29, 2017, in Oral Surgery Oral Medicine Oral Pathology Oral Radiology.

Although definitions vary, leukoplakia—the most common OPMD—generally refers to white lesions of the oral mucosa that cannot be defined as a known disease or disorder and are at an increased risk of experiencing malignant transformation. According to the authors, leukoplakias deemed to be at most risk of progressing to malignancy are often speckled red-and-white lesions, while purely red lesions (erythroplakia) carry the greatest risk. They pointed out that relatively few lesions progress to cancer.

The clinical features strongly associated with an increased risk of experiencing malignant transformation were lesion size larger than 200 square millimeters, nonhomogeneous texture, red or speckled appearance, and location on the tongue or floor of the mouth.

Most studies reviewed by the authors found that the tongue and floor of the mouth had the highest transformation rates, with some variations attributed to population differences in alcohol consumption and tobacco use.

Comparing studies based on the clinical appearance of lesions is difficult for several reasons, the authors wrote. Nevertheless, several systematic reviews and other studies comparing homogeneous and nonhomogeneous leukoplakia indicated that nonhomogeneous lesions were much more likely to progress. For example, a systematic review of 24 studies by Warnakulasuriya and Ariyawardana1 revealed an overall malignant transformation rate of 1.5% to 34%. Eight of these 24 studies compared homogeneous and nonhomogeneous lesions, and the overall transformation rate was 3% for homogeneous lesions and 14.5% for nonhomogeneous lesions (P = .001). The authors pointed out that entirely red lesions, known as erythroplakias, are relatively uncommon, but, according to several studies, they often show evidence of invasive cancer at first biopsy.

Two studies found an association between lesion size and risk of experiencing transformation. A study consisting of 236 patients found that lesions larger than 200 mm2 were more likely than smaller lesions to progress to cancer. Investigators in another study of 50 patients reported that the risk of experiencing transformation was 6 times higher in patients with large confluent lesions that extended over more than 1 anatomic site.
Overall, a medium association was suggested between being older than 50 years and the risk of experiencing transformation.

A study involving 782 patients with leukoplakia found the highest transformation rate (6.4% in 5 years) among those aged 70 through 89 years; in contrast, the transformation rate was only 1% among patients younger than 50 years.

Although OPMDs are less common in women than in men, several investigators reported a higher rate of malignant transformation in women. In their systematic review, Warnakulasuriya and Ariyawardana1 identified 12 studies that examined sex and malignant transformation. In 9 of these studies, the rate of transformation was higher in women than in men; the overall rate was 13.1% in women and 1.7% in men. Despite these findings, “it is still unclear why women are more predisposed to malignant transformation compared with men,” the authors wrote. They assigned a medium association between malignant transformation and being female.

Tobacco use and alcohol consumption are well-established etiologic factors for OPMD development. However, some studies reported a higher rate of malignant transformation of OPMDs in nonsmokers than in smokers. In 1 Swedish study, the cumulative frequency of oral cancer development over 5 years was 3.1% in patients who did not use tobacco compared with 0.4% in smokers. In another study, Ho and colleagues2 evaluated 91 patients with histologically diagnosed epithelial dysplasia, 20 of whom were never smokers, 29 were moderate smokers, and 42 were heavy smokers. After 5 years’ follow-up, 43% of never smokers developed cancer compared with 11% of moderate smokers and 4% of heavy smokers. These data suggest that other factors may be involved in at least some of these cases, wrote the authors. Regarding alcohol consumption, the authors found no evidence of its role as a risk factor for malignant transformation of established lesions.

The standard diagnostic procedure for OPMDs is a biopsy and histologic examination. Cytologic atypia and distorted epithelial architecture are referred to collectively as oral epithelial dysplasia (OED). Pathologists typically grade lesions as mild, moderate, and severe dysplasia on the basis of the extent of architectural and cytologic changes. Clinicians are more likely to intervene when a patient has a moderate or severe OED, whereas they might adopt a wait-and-see approach for lesions exhibiting mild dysplasia. The authors discuss a binary grading system developed by Kujan and colleagues3, as well as the risks of other defined oral lesions.

The authors provide an algorithm for risk assessment that consists of 3 stages: clinical history, clinical examination, and biopsy and histopathologic evaluation. The features at each stage (for example, homogeneous versus nonhomogeneous lesion) are assigned a risk profile, indicating low, medium, or high risk. Although these clinical parameters may offer additional information, histopathologic evaluation remains the standard in the risk assessment of OPMDs.

Read the original article here.

  1. Warnakulasuriya S, Ariyawardana A. Malignant transformation of oral leukoplakia: a systematic review of observational studies. J Oral Pathol Med. 2016;45(3):155-166.
  2. Ho MW, Risk JM, Woolgar JA, et al. The clinical determinants of malignant transformation in oral epithelial dysplasia. Oral Oncol. 2012;48(10):969-976.
  3. Kujan O, Oliver RJ, Khattab A, Roberts SA, Thakker N, and Sloan PP. Evaluation of a new binary system of grading oral epithelial dysplasia for prediction of malignant transformation. Oral Oncol. 2006;42(10): 987–993.

Osteonecrosis of the jaw in patients who switch from bisphosphonates to denosumab

Although bisphosphonates (BP) and denosumab are associated with osteonecrosis of the jaw (ONJ), few data are available regarding the development of ONJ in patients treated with BP and denosumab consecutively. In this retrospective cohort study, researchers evaluated whether ONJ developed more rapidly in patients who switched from BP to denosumab treatment than in those treated with denosumab who were naive to BP. The results were published in the January issue of Oral Surgery Oral Medicine Oral Pathology Oral Radiology.

The study sample comprised 31 patients with ONJ who had received denosumab treatment at a tertiary referral center in Tel-Hashomer, Israel, between 2013 and 2016. Exclusion criteria were the concomitant use of another medication associated with ONJ or insufficient data on denosumab dosage before onset of ONJ symptoms. The researchers also collected demographic data and information about comorbidities and triggering events (such as tooth extraction).

Of the 31 patients in the study, 22 (13 women, 9 men) had been treated with BPs before being switched to denosumab (BP + D), and 9 (1 woman, 8 men) had received denosumab treatment only. Both groups were similar regarding known risk factors for ONJ (that is, age, diabetes mellitus, and smoking).

In the BP + D group, 9 of the 13 women had been treated for bone metastases of breast cancer, and 4 had received treatment for osteoporosis. Six of the 9 men in the BP + D group had received treatment for prostate cancer, 1 for lung cancer, and the remaining 2 for osteoporosis. In contrast, 7 of the 8 men in the denosumab-only group were being treated for bone metastasis of prostate cancer, and 1 was being treated for metastatic lung cancer. The sole woman in the denosumab-only group received treatment for metastatic breast cancer. All patients with cancer received 120 milligrams of denosumab every 4 weeks, and all patients with osteoporosis received 60 mg every 6 months.

The mean duration of intravenous BP treatment (pamidronate or zoledronic acid) for patients with cancer was 22.6 months. Two patients with cancer had received oral BP treatment for osteoporosis before being diagnosed with bone metastasis; their treatment was then changed to denosumab. Patients with osteoporosis received oral BP treatment (alendronate or risedronate) for a mean of 91 months before shifting to denosumab treatment.

The study findings showed a statistically significantly lower number of doses (P = .025) and cumulative doses (P = .018) of denosumab before the onset of ONJ symptoms in the BP + D group than in the denosumab-only group, the authors wrote. Nine patients (41%) in the BP + D group developed ONJ symptoms after receiving 3 or fewer doses of denosumab compared with only 1 patient (11%) in the denosumab-only group.

Of the 31 patients in this study, 8 developed ONJ after a dental surgical procedure (tooth extraction in 7 and implant placement in 1), and 23 developed ONJ spontaneously, with no known triggering event. The researchers found no significant difference in the number or nature of triggering events between the BP + D group and the denosumab-only group.

Because of the small sample size, controlled studies are needed to confirm these findings, the researchers wrote. However, when prescribing antiresorptive agents, physicians should be aware of the possibility of accelerated development of ONJ in patients whose treatment is switched from BP to denosumab.

Read the original article here.

2018 AAOMP and IAOP joint meeting set for June 23-28

Join the American Academy of Oral and Maxillofacial Pathology and the International Association of Oral Pathologists at the joint meeting, “21st Century Diagnostics: Molecular Genetics to Immunohistochemistry,” June 23-June 28, 2018 in Vancouver, BC.
The meeting will feature top speakers from all over the world to speak on topics including:

  • Soft tissue and bone sarcomas of the head and neck with emphasis on ancillary studies to include IHC and molecular.
  • Tumor microenvironment.
  • Challenging cases in head and neck pathology.
  • Dermatologic tumors for oral and maxillofacial pathologists.
  • Case studies involving head and neck radiology.
  • Molecular alterations in head and neck cancer/salivary gland tumors/thyroid cancer with emphasis on diagnosis and treatment.
  • Odontogenic tumors: molecular pathology to personalized medicine.

To register or find more information on the program, schedule, exhibitors, hotel reservations visit

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 and it also encourages your patients to consult with you whenever they have a symptom. 

The 6-panel brochure also 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 18413E before March 16 can save 15 percent on all ADA Catalog products. 


Mark your calendar for the 2018 Joint AAOMP and IAOP meeting
Join AAOMP and the IAOP for our Joint Meeting June 22-June 28, 2018 at the Westin Bayshore Hotel in Vancouver, BC, Canada. Visit for more details.


JADA+ Specialty Scans and JADA+ Scans

JADA+ Specialty Scans and JADA+ Scans are quarterly newsletters updating dentists on the latest research in selected specialties and disciplines in dentistry. ADA Publishing and the consulting editors from the represented specialties and disciplines aggregate and summarize research from previously published materials, each item attributed to its publication of origin. JADA+ Scan specialties and disciplines include endodontics, oral pathology, orthodontics, pediatric dentistry, periodontics, prosthodontics, radiology, cosmetic/esthetic and osseointegration. 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. View past issues here.

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