Hector Lanfranchi

American College of Rheumatology classification criteria for Sjögren's syndrome: a data-driven, expert consensus approach in the Sjögren's International Collaborative Clinical Alliance cohort.

We propose new classification criteria for Sjögrens syndrome (SS), which are needed considering the emergence of biologic agents as potential treatments and their associated comorbidity. These criteria target individuals with signs/symptoms suggestive of SS.

Associations between salivary gland histopathologic diagnoses and phenotypic features of Sjogren's syndrome among 1,726 registry participants.

OBJECTIVE To examine associations between labial salivary gland (LSG) histopathology and other phenotypic features of Sjögrens syndrome (SS). METHODS The database of the Sjögrens International Collaborative Clinical Alliance (SICCA), a registry of patients with symptoms of possible SS as well as those with obvious disease, was used for the present study. LSG biopsy specimens from SICCA participants were subjected to protocol-directed histopathologic assessments. Among the 1,726 LSG specimens exhibiting any pattern of sialadenitis, we compared biopsy diagnoses against concurrent salivary, ocular, and serologic features. RESULTS LSG specimens included 61% with focal lymphocytic sialadenitis (FLS; 69% of which had focus scores of ≥1 per 4 mm²) and 37% with nonspecific or sclerosing chronic sialadenitis (NS/SCS). Focus scores of ≥1 were strongly associated with serum anti-SSA/SSB positivity, rheumatoid factor, and the ocular component of SS, but not with symptoms of dry mouth or dry eyes. Those with positive anti-SSA/SSB were 9 times (95% confidence interval [95% CI] 7.4-11.9) more likely to have a focus score of ≥1 than were those without anti-SSA/SSB, and those with an unstimulated whole salivary flow rate of <0.1 ml/minute were 2 times (95% CI 1.7-2.8) more likely to have a focus score of ≥1 than were those with a higher flow rate, after controlling for other phenotypic features of SS. CONCLUSION Distinguishing FLS from NS/SCS is essential in assessing LSG biopsies, before determining focus score. A diagnosis of FLS with a focus score of ≥1 per 4 mm², as compared to FLS with a focus score of <1 or NS/SCS, is strongly associated with the ocular and serologic components of SS and reflects SS autoimmunity.

Alterations of p53, cyclin D1, rb, and H‐ras in human oral carcinomas related to tobacco use

Epidemiologic studies have indicated that environmental and personal habits, particularly tobacco use and alcohol abuse, are major etiologic factors in the induction and progression of head and neck squamous cell carcinomas (HNSCC). Molecular studies have focused on HNSCC related to smoking but not those associated with smokeless tobacco.

p53, Rb, and cyclin D1 expression in human oral verrucous carcinomas.

The verrucous carcinoma (VC), a tumor with low grade malignancy, appears to be associated with tobacco and human papillomavirus. The pathobiology of these tumors has not been extensively studied, and molecular genetic alterations have not been reported. In this study we investigated by immunohistochemistry the expression of p53, Rb, and cyclin D1 in a series of well‐defined oral VC. Changes in the expression of these genes have been commonly reported in a variety of human tumors.

An early view of the international Sjögren's syndrome registry.

Of the major autoimmune connective tissue diseases, Sjoren’s syndrome (SS) is perhaps the least well understood. Both primary and secondary forms of SS occur, but their phenotypes are not well defined. No less than 10 sets of diagnostic/classification criteria for SS have been applied since 1965 (1–11), but none have been universally adopted or accepted by the American College of Rheumatology. These criteria have often identified patients with similar clinical features, but not necessarily with a common disease process. There is scant longitudinal data on SS. The absence of recognized classification criteria contributes to delays in diagnosis for individual patients and hampers research into SS due to small sample sizes and heterogeneously diagnosed patient populations. To address these issues, the ongoing Sjoren’s International Collaborative Clinical Alliance (SICCA) was funded under a US National Institutes of Health contract beginning in 2003. The SICCA project has the goals of 1) designing and implementing an international SS registry for collecting and storing clinical data and biospecimens; 2) developing standardized classification/diagnostic criteria for SS that are universally applicable; and 3) providing these resources for future studies of SS funded by the NIH or comparable agencies.

Angina bullosa hemorrhagica

Background In 1967, Badham used the term angina bullosa hemorrhagica (ABH) to describe an entity we already knew as traumatic oral hemophlyctenosis (TOH) (1933) and later renamed recurrent oral hemophlyctenosis (ROH) (1971).

The SSB-positive/SSA-negative antibody profile is not associated with key phenotypic features of Sjögren's syndrome

Objective To determine whether the Sjögrens syndrome B (SSB)-positive/Sjögrens syndrome A (SSA)-negative antibody profile is associated with key phenotypic features of SS. Methods Among registrants in the Sjögrens International Collaborative Clinical Alliance (SICCA) with possible or established SS, we compared anti-SSA/anti-SSB reactivity profiles against concurrent phenotypic features. We fitted logistic regression models to explore the association between anti-SSA/anti-SSB reactivity profile and each key SS phenotypic feature, controlling for potential confounders. Results Among 3297 participants, 2061 (63%) had negative anti-SSA/anti-SSB, 1162 (35%) had anti-SSA with or without anti-SSB, and 74 (2%) anti-SSB alone. Key SS phenotypic features were more prevalent and had measures indicative of greater disease activity in those participants with anti-SSA, either alone or with anti-SSB, than in those with anti-SSB alone or negative SSA/SSB serology. These between-group differences were highly significant and not explained by confounding by age, race/ethnicity or gender. Participants with anti-SSB alone were comparable to those with negative SSA/SSB serology in their association with these key phenotypic features. Among SICCA participants classified with SS on the basis of the American-European Consensus Group or American College of Rheumatology criteria, only 2% required the anti-SSB-alone test result to meet these criteria. Conclusions The presence of anti-SSB, without anti-SSA antibodies, had no significant association with SS phenotypic features, relative to seronegative participants. The solitary presence of anti-SSB antibodies does not provide any more support than negative serology for the diagnosis of SS. This serological profile should thus be interpreted cautiously in clinical practice and potentially eliminated from future classification criteria.

Genome-Wide Association Analysis Reveals Genetic Heterogeneity of Sjögren's Syndrome According to Ancestry

The Sjögrens International Collaborative Clinical Alliance (SICCA) is an international data registry and biorepository derived from a multisite observational study of participants in whom genotyping was performed on the Omni2.5M platform and who had undergone deep phenotyping using common protocol‐directed methods. The aim of this study was to examine the genetic etiology of Sjögrens syndrome (SS) across ancestry and disease subsets.

Immunocytochemical detection of carcinoembryonic antigen in salivary gland tumors

The immunoperoxidase method was applied for carcinoembryonic antigen (CEA) detection in biopsy specimens of salivary gland tumors. 9 out of 10 adenoidcystic carcinomas revealed a strong and abundant reaction in tumoral glands. 10 other specimens of pleomorphic adenomas showed weak staining in the areas of epithelial proliferation. Normal glands adjacent to the tumor mass revealed a weak but constant reaction on the luminal border. As in other types of gland tumor, the quantitative estimation of CEA production by salivary gland tumors may be useful in the monitoring of recurrencies.

Oral and oropharynx cancer in South America: Incidence, mortality trends and gaps in public databases as presented to the Global Oral Cancer Forum

Objectives: To describe the incidence and mortality of oral and oropharynx cancers in South America using available public databases and to discuss the main pitfalls for acquiring reliable data. Methods: The incidence data for oral cavity and oropharynx cancers for South America were obtained from Cancer Incidence in Five Continents/International Agency for Research on Cancer for the period 1998–2007. Mortality rates in South America were obtained from the World Health Organization/IARC database for the period 1999–2012. The number of cases for Brazil was obtained from the National Cancer Institute/missing stage for the period 2000–2010, whereas the São Paulo cancer registry was used to collect data from the most populated state in Brazil for the period 2000–2008. Results: The incidence of oral and oropharynx cancers in South America varied, with the highest rates observed in Brazil among males. The mortality data in selected South American countries ranged from 0.72 to 6.04/100,000 and the proportion of ill-defined deaths in South America varied from 5.0% to 22.0%. Mortality trends for males decreased about 2.5% in most of the countries, excluding Brazil, whereas among females, a significant decrease occurred only in Colombia, with an increase in Brazil and Peru. Conclusion: Although there is a lack of reliable databases in South America, the available data demonstrate a decrease in mortality trends in most countries and the highest incidence in Brazil. The development and improvement of national cancer public databases in South America are highly desirable and necessary to better understand the characteristics and distribution of these neoplasms.