MALT lymphoma in labial salivary gland biopsy from Sjögren syndrome: importance of follow-up in early detection.

Mucosa-associated lymphoid tissue (MALT) lymphomas are known to occur in Sjögren syndrome (SS) patients, but reported cases in labial salivary glands (LSG) are rare. We report a case of 60-year-old female patient with SS who developed MALT lymphoma in the labial salivary glands during a 2-year time interval when she was participating in the Sjögren's International Clinical Collaborative Alliance, an ongoing longitudinal multisite observational study funded by the National Institutes of Health of the United States. At follow-up exam, LSG biopsy showed atypical diffuse infiltration by mononuclear cells of variable size and atypical nuclei affecting the whole specimen with destruction of glandular architecture, leading to a diagnosis of B-cell MALT lymphoma. Computerized tomography and bone marrow biopsy failed to show additional evidence of disease. Clinical, serologic, ocular, histologic and immunohistochemical findings are presented. A "watch and wait" policy was adopted with regular examinations.

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.

OBJECTIVE: We propose new classification criteria for Sjögren's 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. METHODS: Criteria are based on expert opinion elicited using the nominal group technique and analyses of data from the Sjögren's International Collaborative Clinical Alliance. Preliminary criteria validation included comparisons with classifications based on the American­European Consensus Group (AECG) criteria, a model-based "gold standard"obtained from latent class analysis (LCA) of data from a range of diagnostic tests, and a comparison with cases and controls collected from sources external to the population used for criteria development. RESULTS: Validation results indicate high levels of sensitivity and specificity for the criteria. Case definition requires at least 2 of the following 3: 1) positive serum anti-SSA and/or anti-SSB or (positive rheumatoid factor and antinuclear antibody titer >1:320), 2) ocular staining score >3, or 3) presence of focal lymphocytic sialadenitis with a focus score >1 focus/4 mm2 in labial salivary gland biopsy samples. Observed agreement with the AECG criteria is high when these are applied using all objective tests. However, AECG classification based on allowable substitutions of symptoms for objective tests results in poor agreement with the proposed and LCA-derived classifications. CONCLUSION: These classification criteria developed from registry data collected using standardized measures are based on objective tests. Validation indicates improved classification performance relative to existing alternatives, making them more suitable for application in situations where misclassification may present health risks.

Granuloma gigantocelular central del maxilar inferior: Presentación de un caso pediátrico / Giant cell granuloma of the lower jaw: Description of a pediatric case

El granuloma gigantocelular central (GGCC), es una lesión tumoral o seudotumoral, infrecuente de los huesos de la cabeza y cuello, que afecta más frecuentemente los maxilares. Su etiología y patogenia son poco conocidas, sus características histológicas son benignas y su comportamiento biológico puede ser agresivo localmente. Presentamos el caso de un niño de 6 años con esta afección y realizamos una revisión de la entidad y sus diagnósticos diferenciales con otras lesiones de los maxilares.

Giant Cell Granuloma (GCG) is an uncommon condition affecting the bones of the head and neck. The ethiology and pathophysiology are not completely understood. The histlogic characteristics of GCG are benign, but its biologic behavior could locally aggressive. We describe the case of a 6 year-old boy with GCG and performed a review of the entity ant their differential diagnosis with other lesions of the maxillary bones.

Biopsy vs. superficial scraping: detection of human papillomavirus 6, 11, 16, and 18 in potentially malignant and malignant oral lesions.

BACKGROUND: Several epidemiologic studies have shown a broad variation in the prevalence of human papillomavirus (HPV) in oral precancerous tissues and oral carcinomas. METHODS: Biopsies and superficial scrapes of lesions, clinically suspected of HPV infection, were taken from patients with potentially malignant and malignant oral lesions, and subject to HPV DNA detection by PCR-Southern blot analysis. RESULTS: From 22 patients with potentially malignant and malignant lesions analyzed, 41% of the biopsies were HPV DNA positive, whereas 95-100% of the superficial scrapes were positive (McNemar, P < 0.0001). Clinical presumption of HPV infection detected 67% (P < 0.0001) of the HPV DNA positive cases compared with 48% (P < 0.0001) determined by cytology and histopathology. The prevalence of HPV 6, 11, 16 and 18 in the oral mucosa was studied in 59 individuals. While 9% of normal controls were HPV DNA positive, 100% of the patients with potentially malignant and malignant lesions were HPV DNA positive, and the prevailing genotype was HPV 16 followed by HPV 18. CONCLUSIONS: The higher HPV DNA detection rate in superficial oral scrapes than in biopsies suggests that accurate epidemiological information on oral HPV infection/oral carcinogenesis depends not only on the DNA detection technique, but also on the tissue/cell sampling procedure.

Use of correction procedures in ploidy analysis of oral carcinomas.

Ploidy analysis is an aid in the diagnosis and evaluation of prognosis of tumors. Image analysis is a relatively simple technique to assess ploidy that can be carried out with accessible equipment. However, it requires the use of accurate technical procedures to avoid methodological errors that may bias the measurements. We previously developed two procedures that are simple to apply in routine work and serve to correct the errors derived from the measurement of large nuclei that are not fully contained in the thickness of the section and those derived from non-specific background readings. In the present study we applied these corrections to the retrospective ploidy analysis of a series of 67 patients with oral carcinoma with a follow-up time of 18 months. Thirty-four patients were alive at the end of the study, 33 were deceased. The ploidy values and the malignancy indices corresponding to the deceased and live patients with TNM stage III and IV carcinomas at the time of biopsy were significantly different. There were no significant differences in ploidy values between live and deceased patients with TNM stage I and II at the time of biopsy. The corrections improved the sensitivity of the method and thus the statistical significance of the data. These data suggest that the method proposed may be of use to estimate lesion evolution, in particular in patients with advanced oral squamous cell carcinomas.

Use of correction procedures in ploidy analysis of oral carcinomas.

Ploidy analysis is an aid in the diagnosis and evaluation of prognosis of tumors. Image analysis is a relatively simple technique to assess ploidy that can be carried out with accessible equipment. However, it requires the use of accurate technical procedures to avoid methodological errors that may bias the measurements. We previously developed two procedures that are simple to apply in routine work and serve to correct the errors derived from the measurement of large nuclei that are not fully contained in the thickness of the section and those derived from non-specific background readings. In the present study we applied these corrections to the retrospective ploidy analysis of a series of 67 patients with oral carcinoma with a follow-up time of 18 months. Thirty-four patients were alive at the end of the study, 33 were deceased. The ploidy values and the malignancy indices corresponding to the deceased and live patients with TNM stage III and IV carcinomas at the time of biopsy were significantly different. There were no significant differences in ploidy values between live and deceased patients with TNM stage I and II at the time of biopsy. The corrections improved the sensitivity of the method and thus the statistical significance of the data. These data suggest that the method proposed may be of use to estimate lesion evolution, in particular in patients with advanced oral squamous cell carcinomas.

Use of correction procedures in ploidy analysis of oral carcinomas

Ploidy analysis is an aid in the diagnosis and evaluation of prognosis of tumors. Image analysis is a relatively simple technique to assess ploidy that can be carried out with accessible equipment. However, it requires the use of accurate technical procedures to avoid methodological errors that may bias the measurements. We previously developed two procedures that are simple to apply in routine work and serve to correct the errors derived from the measurement of large nuclei that are not fully contained in the thickness of the section and those derived from non-specific background readings. In the present study we applied these corrections to the retrospective ploidy analysis of a series of 67 patients with oral carcinoma with a follow-up time of 18 months. Thirty-four patients were alive at the end of the study, 33 were deceased. The ploidy values and the malignancy indices corresponding to the deceased and live patients with TNM stage III and IV carcinomas at the time of biopsy were significantly different. There were no significant differences in ploidy values between live and deceased patients with TNM stage I and II at the time of biopsy. The corrections improved the sensitivity of the method and thus the statistical significance of the data. These data suggest that the method proposed may be of use to estimate lesion evolution, in particular in patients with advanced oral squamous cell carcinomas.

Image analysis of p53 and cyclin D1 expression in premalignant lesions of the oral mucosa.

OBJECTIVE: The expression of p53 and cyclin D1 proteins was analyzed by image analysis in oral premalignant lesions and normal oral mucosa. STUDY DESIGN: Punch biopsies from the normal oral mucosa were obtained from 20 normal donors and 41 patients with oral dysplastic leukoplakias. After controlled formaldehyde fixation and paraffin embedding, immunohistochemistry was used to detect cyclin D1 and p53. Image analysis was performed using stain intensity levels established by determining color thresholds (nuclear score) in the basal and parabasal layers. RESULTS: Analysis of sections showed a similar pattern: only two normal donors had a few intensely positive p53 cells in the basal layer of the floor of the mouth and the tongue epithelia. Similarly, only three donors had intensely positive cyclin D1 cells in the normal epithelia of the same sites. Most cells fell in the range of negative or marginal stain (lower quartiles or terciles of nuclear score). These data on normal mucosa were compared with low grade oral leukoplakias (LGD) with mild to moderate dysplasia and with high grade leukoplakias (HGD) with severe dysplasia. Both markers were differentially expressed in precursor lesions versus normal epithelia. Statistical analysis of our data shows that the intensity of the immunohistochemical stain, as reflected in the nuclear scores of p53, is a reliable parameter that can differentiate between LGD and HGD of the oral mucosa. This was especially true when higher nuclear scores were compared. In contrast, low nuclear scores are more effective in differentiating normal epithelia from dysplastic epithelia. Although cyclin D1 immunohistochemistry does not stain as intensely as p53 stain, similar conclusions can be derived from those data. CONCLUSION: Image analysis of these two markers proved useful in distinguishing normal oral epithelia from low grade and high grade leukoplakias. With further developments in this field it is hoped that image analysis procedures could be used in different types of studies in which variations of protein expression in tissue sections could have prognostic implications or could be useful to determine subtle effects of curative or preventive treatment.

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). OBJECTIVES: The objective of this study was to review and discuss the literature, and to report 54 new cases seen between 1989 and 1996. MATERIALS AND METHODS: Fifty-four patients were thoroughly assessed to determine the clinical features, histology, etiology, pathogenesis, differential diagnosis, and therapy. RESULTS: In 35 patients (64.8%), the lesions predominated on the palate and in nine (16.6%) on the oral mucosa. The incidence was similar in both sexes (women, 52%; men, 48%) and the condition affected mostly the 51-70-year age group. ABH was never documented in children under 10 years of age. In 24 cases (44.4%), diabetes mellitus, hyperglycemia, and/or a family history of diabetes was found. CONCLUSIONS: ABH is a disorder more common than the literature would suggest. Although the causes may be multiple (mucosal trauma, inhaled corticosteroids), the available data indicate that, in these patients, the presence of an alteration in glucose metabolism should be considered.

Alterations of p53, cyclin D1, Rb, and H-ras in human oral carcinomas related to tobacco use.

BACKGROUND: 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. METHODS: The authors studied immunohistochemical evidence of alterations of p53, cyclin D1, and Rb in 34 human oral carcinomas related to tobacco use. They also examined p53 and H-ras using single strand conformation polymorphism (SSCP) and sequencing analysis. RESULTS: Overexpression of cyclin D1 was found in 41% of cases, and accumulation of p53 was found in 59%. Only 9% of the samples did not show Rb staining. In SSCP and sequencing analysis, 17 cases showed mutations in the conserved region of the p53 gene. No mutations were detected in codons 12, 13, or 61 of the H-ras gene. CONCLUSIONS: Overexpression of cyclin D1 and p53 mutations are common alterations in HNSCC. In contrast, the loss of Rb function seems to occur infrequently, and mutations in the H-ras gene apparently do not play a role in this cancer. HNSCC associated with smokeless tobacco contained the same alterations as those related to smoking.

A comparative study of oral lichen planus and leukoplakia in two Argentine populations.

Oral Lichen Planus and Leukoplakia are two precancerous lesions of great relevance in oral pathology. A total of 4183 patients from the National University of Córdoba (UNC) and 4838 patients from the University of Buenos Aires (UBA) who had been admitted to the corresponding Oral Pathology Departments were analyzed. Of the total number of patients, 476 corresponded to Lichen Planus cases and 418 to Leukoplakia cases. Of the 476 Lichen Planus cases, 330 came from UBA and 146 from UNC, whereas of the 418 cases of Leukoplakia, 284 came from UNC and 134 from UBA. These differences were statistically significant (p < 0.02). Distribution according to sex and age was similar for Lichen Planus and Leukoplakia patients from both Oral Pathology Departments. The association between diabetes and Lichen Planus was similar for both centers, 11.5% for UNC and 14% for UBA. Similarly, no differences were found in terms of the association with tobacco consumption and dental microtrauma. Twenty-two percent of UNC patients were smokers whereas only 11% of UBA patients were smokers. This finding could explain the larger amount of Leukoplakia in UNC. The differences in the incidence of Lichen Planus could be attributed to the fact that the Buenos Aires population is under greater stress and the higher incidence of Leukoplakia in UNC could be related to the smoking habits of this population.

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

BACKGROUND: 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. METHODS: We studied 29 cases of VC, fixed in formalin and embedded in paraffin. Immunohistochemistry was carried out using the avidin-biotin immunoperoxidase technique. Polyclonal antibody CM-1 was used for p53, a rabbit polyclonal human RB antibody, Rb-WL-1 antibody for Rb and a rabbit polyclonal human cyclin D antibody for cyclin D1. RESULTS: Positive p53 expression (protein accumulation) was detected in 15 of the 29 VC analyzed. In some cases, p53-positive areas were small foci but in most of the cases extensive positive areas were observed. None of the cases studied showed alterations of Rb protein. The expression of cyclin D1 was determined in 18 cases of VC. Positive nuclear immunostaining was seen in 11 cases. CONCLUSIONS: p53 protein accumulation is frequently observed in these tumors suggesting possible mutations of this gene in VC. Overexpression of cyclin D1 but no alterations of Rb staining were also observed in this low grade tumor suggesting that Rb may be functionally inactivated by overexpression of cyclin D1 or HPV infection.

Study of the vascular pattern in oral lichen planus.

Oral Lichen Planus is a relatively frequent disease. Its etiopathogenesis is still unknown and it can undergo malignant transformation during its evolution. Thus, data which could contribute to the knowledge of the biology of this disease are particularly significant. The present study involves a quantitative evaluation of the vascular pattern of oral lichen planus. A portion of biopsy specimens taken for histopathologic diagnosis was processed to mark vascular walls using the histoenzymic technique for ATPase activity demonstration. Stained Sections were then evaluated in a semi-automatic magnetic image analyser. The stereologic parameters studied, showed there is no vascular increase in lichen with regard to normal mucosae or leukoplakias, since the number of vascular walls did not show significant differences. Instead, a significant increase was observed in the vascular area. The association of these parameters, indicates that lichen is a more congestive lesion than the other two conditions studied. These findings indicate that the modifications of the vascular pattern could play a role in the etiopathogenesis of oral lichen planus and suggest that the observation of these changes could be a useful element in the histopathologic diagnosis.

Nucleolar organizer regions in lining epithelium adjacent to squamous cell carcinoma of human oral mucosa.

BACKGROUND: The value of silver staining of nucleolar organizer regions (AgNOR) counts as a diagnostic aid has been reported for several neoplastic entities. Previous studies have proved the value of the morphometric evaluation of AgNOR in the detection of incipient cellular alterations. METHODS: A morphometric analysis of AgNORs was performed in oral mucosa epithelium adjacent to squamous cell carcinoma compared with normal mucosa epithelium and the carcinomatous parenchyma. RESULTS: Highly statistically significant differences in all 5 AgNOR-related parameters assessed were found between normal mucosa and mucosa adjacent to cancer. Conversely, the corresponding nuclear parameters failed to exhibit significant differences. The parameter AgNOR contour index plotted for individual cases affords a cutoff value that could prove useful in identifying epithelia at early stages of transformation. CONCLUSIONS: AgNOR evidenced significant variations in epithelium adjacent to oral squamous cell carcinoma, which did not exhibit morphologic signs of atypia. Based on this study, AgNOR would be a quantitative, discriminative aid, easy to monitor in a pathology laboratory, in detecting incipient cellular alterations. These findings contribute to the issue of early diagnosis and to the knowledge of tumoral growth.

Inhibition of benzoyl peroxide-induced tumor promotion and progression by copper(II)(3,5-diisopropylsalicylate)2.

The ability of a biomimetic superoxide dismutase agent, copper(II)(3,5-diisopropylsalicylate)2 (CuDIPS), to modulate benzoyl peroxide (BzPo)-induced tumor promotion and progression in mouse skin multistage carcinogenesis was evaluated. The results showed a significant inhibition of tumor incidence by CuDIPS pretreatment during promotion-progression. Different types of tumors were developed: papillomas, keratoacanthomas and squamous cell carcinomas. There was a significant increase in the keratoacanthoma-papilloma ratio when the period of treatment with BzPo was prolonged, which was inhibited by CuDIPS pretreatment. CuDIPS induced a significant inhibition of malignant conversion. Our results suggest that reactive oxygen species could be important in BzPo-induced promotion and progression.

Simultaneous PAGE, immunoblotting, and immunohistochemical analysis of differentiation associated keratins in lesions of the oral mucosa.

The expression of differentiation associated high PM Keratin polypeptides of the oral mucosa lesions were studied by immunohistochemical and immunoblotting techniques applied to adjacent sections of each biopsy specimen. The material studied included specimens of leukoplakia, verrucous carcinoma, squamous cell carcinoma, adenocarcinoma and keratoacanthoma. Little or no expression of 65-67 Kd keratins was evident in squamous cell carcinoma and adenocarcinoma. Hyperkeratotic (both benign and dysplastic) lesions such as verrucous carcinoma, leukoplakia, and keratoacanthoma, showed great variations in the intensity of 65-67 bands and a very irregular immunohistochemical staining pattern. Increased amounts of horny substance was usually accompanied by absence of, or decreased expression of 65-67 Kd keratins, thus indicating a change in the polypeptide composition of the horny layer in pathological conditions of the oral epithelium.

Simultaneous PAGE, immunoblotting, and immunohistochemical analysis of differentiation associated keratins in lesions of the oral mucosa.

The expression of differentiation associated high PM Keratin polypeptides of the oral mucosa lesions were studied by immunohistochemical and immunoblotting techniques applied to adjacent sections of each biopsy specimen. The material studied included specimens of leukoplakia, verrucous carcinoma, squamous cell carcinoma, adenocarcinoma and keratoacanthoma. Little or no expression of 65-67 Kd keratins was evident in squamous cell carcinoma and adenocarcinoma. Hyperkeratotic (both benign and dysplastic) lesions such as verrucous carcinoma, leukoplakia, and keratoacanthoma, showed great variations in the intensity of 65-67 bands and a very irregular immunohistochemical staining pattern. Increased amounts of horny substance was usually accompanied by absence of, or decreased expression of 65-67 Kd keratins, thus indicating a change in the polypeptide composition of the horny layer in pathological conditions of the oral epithelium.

Simultaneous PAGE, immunoblotting, and immunohistochemical analysis of differentiation associated keratins in lesions of the oral mucosa

The expression of differentiation associated high PM Keratin polypeptides of the oral mucosa lesions were studied by immunohistochemical and immunoblotting techniques applied to adjacent sections of each biopsy specimen. The material studied included specimens of leukoplakia, verrucous carcinoma, squamous cell carcinoma, adenocarcinoma and keratoacanthoma. Little or no expression of 65-67 Kd keratins was evident in squamous cell carcinoma and adenocarcinoma. Hyperkeratotic (both benign and dysplastic) lesions such as verrucous carcinoma, leukoplakia, and keratoacanthoma, showed great variations in the intensity of 65-67 bands and a very irregular immunohistochemical staining pattern. Increased amounts of horny substance was usually accompanied by absence of, or decreased expression of 65-67 Kd keratins, thus indicating a change in the polypeptide composition of the horny layer in pathological conditions of the oral epithelium.

Morphometric study of nucleolar organizer regions in human oral normal mucosa, papilloma and squamous cell carcinoma.

A morphometric study of nucleolar organizer regions (NOR) was performed to analyze their distribution, volume, number and shape in the different strata of human normal oral mucosa epithelium and papilloma and in squamous cell carcinoma employing microphotographs of silver-stained paraffin sections. The different NOR-related parameters evidenced significant differences between normal mucosa, papilloma and squamous cell carcinoma. The functional polarity of normal mucosa epithelium and of papilloma is also evidenced in terms of NOR-related parameters. The discriminative value of certain NOR parameters was demonstrated.

Immunodetection of involucrin in lesions of the oral mucosa.

The immunoperoxidase method for involucrin detection was applied to the study of the maturation of epithelial lesions of the oral mucosa that included specimens of leukoplakia, lichen planus, verrucous carcinoma, carcinoma in situ and invasive carcinoma. Areas of orthokeratinized, parakeratinized, and non-keratinized normal mucosa were also studied. Normal orthokeratinized epithelia showed intracytoplasmic or pericellular staining in the suprabasal epithelial layers in a pattern similar to that of the normal epidermis. Parakeratinized and non-keratinized epithelia were less stained. Intense staining was observed in leukoplakia, whereas the staining of lichen planus was less intense but exhibited a more homogeneous pericellular staining pattern than leukoplakia. Verrucous carcinoma was markedly and very irregularly stained. Carcinomas in situ and invasive carcinoma exhibited a slightly positive and patchy reaction. The distribution patterns of involucrin in the lesions correlated very well with the degree of epithelial differentiation. In addition, irregular patchy distribution correlated with the degree of atypia, and was especially evident in carcinomas.