Objective: To evaluate the inter-observer agreement of the severity of oral epithelial dysplasia in oral leukoplakia, providing a theoretical basis for the development of a more objective grading system. Methods: This study included 60 digital pathological slides of oral leukoplakia from Oral Medicine Department of West China Hospital of Stomatology, Sichuan University, and 239 tissue microarray images of oral leukoplakia from State Key Laboratory of Oral Diseases, Sichuan University, to evaluate the agreement of grading. Besides, 1 000 patches were generated from the 60 digital pathological slides and were divided into 500 small-sized patches (224 pixel×224 pixel) and 500 large-sized patches (1 024 pixel×1 024 pixel), to evaluate the agreement of feature detection. Gradings and feature detections were completed by three pathological experts from the oral pathology departments of two Grade 3, Class A stomatological hospitals in China. Kappa coefficient was used to quantify the inter-observer agreement among pathologists. Results: Minimal agreement was found in the grading of oral epithelial dysplasia among pathologists (Kappa=0.30 in the pathological slide group, Kappa=0.30 in the tissue microarray group). None agreement was found in feature detection within the small-sized patches group (median Kappa=0.14 for architectural features, median Kappa=0.18 for cytological features), and minimal agreement was found in feature detection within the large-sized patches group (median Kappa=0.25 for architectural features, median Kappa=0.25 for cytological features). Conclusions: Generally, the agreement of grading and feature detection of oral epithelial dysplasia in oral leukoplakia is poor. Development of a more objective grading system of oral epithelial dysplasia based on artificial intelligence may be helpful to improve the agreement.
Artificial Intelligence ; China ; Humans ; Leukoplakia, Oral ; Observer Variation ; Precancerous Conditions

dysplasia is a lesion similar to oral lichen planus with epithelial dysplasia. It can be clinically mistaken for oral lichen planus, but has histologic features of dysplasia and a true malignant predisposition. It is not a variant or transitional form of lichen planus but, instead, represents a distinct entity that has a true potential for malignant transformation. In addition to abnormal epithelial maturation and cytology, lichenoid dysplasia exhibits other histologic features that separate it from oral lichen planus. Lichenoid dysplasia and lichen planus share many clinical and microscopic features, leading to the frequent misdiagnosis of unrecognized lichenoid dysplasia as lichen planus. We experienced a case of lichenoid dysplasia in the oral mucosa. We treated this patient with surgical excision. The patient has now been followed for two months. It is important to recognize this precancerous condition and inspect the excision site and remaining oral mucosa during long-term follow-up.]]>
Diagnostic Errors ; Follow-Up Studies ; Humans ; Leukoplakia ; Lichen Planus ; Lichen Planus, Oral ; Mouth Mucosa ; Precancerous Conditions

Humans ; Leukoplakia, Oral ; diagnosis ; therapy ; Lichen Planus, Oral ; diagnosis ; therapy ; Mouth Neoplasms ; prevention & control ; Oral Submucous Fibrosis ; diagnosis ; therapy ; Precancerous Conditions ; diagnosis ; therapy

PURPOSE: This study was performed in order to determine the histologic features, incidence & frequency of the Aberrant Crypt Foci (ACFs) including mucosal abnormalities arising in the sporadic colonic cancer. MATERIALS AND METHODS: We investigated the proximal and distal colonic mucosa surrounding the tumor in 22 cases (right colon 7 cases and left colon 15 cases) of resected colonic adenocarcinoma specimen. The methylene blue- stained colonic mucosa was examined in en face preparations and rolled totally. The rolled colonic mucosa was embedded in paraffin and examined by using 4micrometer thick serial sections. RESULTS: We found one hundred twenty two ACFs. The 97 foci (78.7%) were simple hypertrophic foci (SH), composed of more elongated and larger crypts than normal with apical branching associated with goblet cell hyperplasia. The 17 foci (13.9%) were hyperplastic foci (HP) resembling hyperplastic polyp, and 7 (5.7%) were adeno matous foci (AD) while 2 (1.6%) were adenomatous foci with dysplasia (Dys). The mean number of ACFs/cm of the examined mucosa were 0.18+/-0.21 and were higher in the left colon than in the right colon (0.22+/-0.24 vs. 0.10+/-0.10). Immunohistochemical stains for p53 and Ki-67 in these foci revealed strong and upper cryptal staining patterns in AD and Dys of ACFs, like that of neoplasia or preneoplastic condition. However, the staining intensities in SH and HP of ACFs were equal to or lower than that of normal crypts. CONCLUSION: These results suggest that grossly defined ACFs include reactive process and the majority of ACFs are induced by simple reactive alteration without preneoplastic potential; and two types of ACFs (AD and Dys) are more likely to be direct precursors of colon tumors than SH or HP.
Aberrant Crypt Foci* ; Adenocarcinoma* ; Colon ; Colonic Neoplasms ; Colorectal Neoplasms ; Coloring Agents ; Goblet Cells ; Hyperplasia ; Incidence ; Mucous Membrane* ; Paraffin ; Polyps ; Precancerous Conditions

OBJECTIVETo investigate the preventive effect of genistein on the malignant transformation of oral leukoplakia in hamster cheek pouch.

METHODSSixty male Syrian golden hamsters were randomly divided into 4 groups, with two of 20 and two of 10. DMBA solution (0.5% in acetone) was applied topically to the left cheek pouch of male Syrian golden hamsters in group A and B, while animals in group C were painted with acetone, 3 times a week for 6 weeks. For the next 12 weeks, animals in group B received genistein (10 mg.kg(-1).d(-1)) daily by gavage; animals in group A and C received same volume of saline; animals in group D serving as blank control. At the end of the experiment, animals were sacrificed and tissue samples were collected for histopathological examination.

RESULTSNo significant differences in the tumor latency and tumor incidence were observed between the control and genistein treated group.

CONCLUSIONSNo inhibitory effect of genistein on the transformation of oral leukoplakia was observed in hamster.

Animals ; Cricetinae ; Genistein ; pharmacology ; therapeutic use ; Leukoplakia, Oral ; pathology ; prevention & control ; Male ; Mesocricetus ; Mouth Mucosa ; drug effects ; pathology ; Precancerous Conditions ; pathology ; prevention & control

Oral cancer has a tendency to be detected at late stage which is detrimental to the patients because of its high mortality and morbidity rates. Early detection of oral cancer is therefore important to reduce the burden of this devastating disease. In this review article, the most common oral precancerous lesions are discussed and the importance of early diagnosis is emphasized. In addition, the most common non-invasive oral cancer devices that can aid the general practitioners in early diagnosis are also discussed.
Cell Transformation, Neoplastic ; classification ; Coloring Agents ; Early Detection of Cancer ; instrumentation ; methods ; Fluorescence ; Humans ; Leukoplakia, Oral ; diagnosis ; Luminescence ; Mouth Neoplasms ; diagnosis ; Precancerous Conditions ; diagnosis

Optical spectroscopy devices are being developed and tested for the screening and diagnosis of oral precancer and cancer lesions. This study reports a device that uses white light for detection of suspicious lesions and green-amber light at 545 nm that detect tissue vascularity on patients with several suspicious oral lesions. The clinical grading of vascularity was compared to the histological grading of the biopsied lesions using specific biomarkers. Such a device, in the hands of dentists and other health professionals, could greatly increase the number of oral cancerous lesions detected in early phase. The purpose of this study is to correlate the clinical grading of tissue vascularity in several oral suspicious lesions using the Identafi(®) system with the histological grading of the biopsied lesions using specific vascular markers. Twenty-one patients with various oral lesions were enrolled in the study. The lesions were visualized using Identafi(®) device with white light illumination, followed by visualization of tissue autofluorescence and tissue reflectance. Tissue biopsied was obtained from the all lesions and both histopathological and immunohistochemical studies using a vascular endothelial biomarker (CD34) were performed on these tissue samples. The clinical vascular grading using the green-amber light at 545 nm and the expression pattern and intensity of staining for CD34 in the different biopsies varied depending on lesions, grading ranged from 1 to 3. The increase in vascularity was observed in abnormal tissues when compared to normal mucosa, but this increase was not limited to carcinoma only as hyperkeratosis and other oral diseases, such as lichen planus, also showed increase in vascularity. Optical spectroscopy is a promising technology for the detection of oral mucosal abnormalities; however, further investigations with a larger population group is required to evaluate the usefulness of these devices in differentiating benign lesions from potentially malignant lesions.
Adult ; Aged ; Aged, 80 and over ; Antigens, CD34 ; analysis ; Biomarkers, Tumor ; analysis ; Biopsy ; methods ; Carcinoma, Squamous Cell ; blood supply ; diagnosis ; pathology ; Erythroplasia ; diagnosis ; pathology ; Female ; Humans ; Immunohistochemistry ; Leukoplakia, Oral ; blood supply ; diagnosis ; pathology ; Lichen Planus, Oral ; diagnosis ; pathology ; Male ; Middle Aged ; Mouth Neoplasms ; blood supply ; diagnosis ; pathology ; Neoplasm Grading ; Optical Imaging ; methods ; Pilot Projects ; Precancerous Conditions ; blood supply ; diagnosis ; pathology ; Spectrometry, Fluorescence ; methods ; Young Adult

OBJECTIVETo investigate the transmutation and significance of integrin-linked kinase (ILK) in oral leukoplakia and early invasive squamous cell carcinoma.

METHODSImmunohistochemistry accompanied with periodic acid Schiff reaction (PAS) histochemistry was applied to detect the expression of ILK in 19 normal oral mucosa, 43 simple hyperplasia, 84 epithelial dysplasia, 54 early invasive carcinoma.

RESULTSAmong the oral leukoplakia and early invasive squamous cell carcinoma, dramatic positive expression of ILK was found in 163/181 (90%), but was negative in normal mucosa. ILK staining in stroma exhibited a significantly direct correlation with the exacerbated epithelial dysplasia (chi(2) = 41.585, P < 0.001). Along with the oral carcinogenesis, there was an obvious tendency of change-overed ILK staining from superfacial to the basal orientation, the stratum basale diverted into positive, and compared with scattering in cytoplasm, the location of ILK was prone to cytomembrane in epithelium. In severe dysplasia and carcinoma in situ, there was a positive correlation between the basal layer and stroma expression of ILK (P = 0.029). It was not only a weaker tincture of ILK in cancer nest than lesional epithelia, but also an augmentation of stroma staining in early invasive squamous cell carcinoma [76% (41/54)] by contrast with severe dysplasia [45% (18/40)].

CONCLUSIONSThe pivotal role of ILK in the regulation of oral carcinogenesis is considerable, however, the precise mechanisms through which ILK affects cellular processes remain to be fully characterized.

Carcinoma, Squamous Cell ; metabolism ; pathology ; Epithelium ; metabolism ; pathology ; Humans ; Hyperplasia ; Immunohistochemistry ; Leukoplakia, Oral ; metabolism ; pathology ; Mouth Mucosa ; metabolism ; pathology ; Mouth Neoplasms ; metabolism ; pathology ; Periodic Acid-Schiff Reaction ; Precancerous Conditions ; metabolism ; pathology ; Protein-Serine-Threonine Kinases ; metabolism

OBJECTIVETo investigate the roles of surviving and caspase-3 in the development of oral cancer.

METHODSArchival tissue sections of 17 oral squamous cell carcinoma (OSCC), 28 oral leukoplakia with dysplasia, 10 normal oral mucosa were obtained from Capital Medical University School of Stomatology for immunohistochemical staining of markers of survivin and caspase-3. The cell apoptosis was detected with terminal deoxynucleotidyl transferase-mediated nucleotide shift enzyme (TdT) mediated d-UTP end labeling (TUNEL). Positively stained cells were counted and analyzed statistically to determine potential relationship between survivin, caspase-3 and cell apoptosis.

RESULTSThe expression of survivin was faint or negative in normal epithelial cells. The average positive rate of survivin was (1.05 ± 1.21)% in control group and (21.89 ± 10.45)% in OSCC. Caspase-3 was expressed in all the normal mucosa,but it obviously down-regulated in dysplasia and OSCC. The apoptosis index (AI) decreased from (0.89 ± 0.46)% in normal mucosa to (0.21 ± 0.12)% in OSCC.

CONCLUSIONSBoth survivin and caspase-3 are associated with carcinogenesis of the oral mucosa. Survivin may restrain cell apoptosis by inhibiting caspase-3.

Apoptosis ; Carcinoma, Squamous Cell ; enzymology ; metabolism ; pathology ; Caspase 3 ; metabolism ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Leukoplakia, Oral ; enzymology ; metabolism ; pathology ; Mouth Mucosa ; enzymology ; metabolism ; Mouth Neoplasms ; enzymology ; metabolism ; pathology ; Precancerous Conditions ; enzymology ; metabolism ; pathology

OBJECTIVETo investigate the histological features of oral leukoplakia which underwent malignant transformation and its correlation with the clinical manifestation.

METHODSA total of 1832 cases of oral leukoplakia were reviewed and the clinicopathological characteristics of malignant transformation were analyzed.

RESULTSMalignant transformation occurred in 85 cases (4.6%) of the 1832 cases. Thirty cases (2.1%) of 1404 cases with simple epithelial hyperplasia had malignant transformation. Fifty-five cases (12.9%) in 428 cases with epithelial dysplasia were transformed to malignancy, especially in the cases with moderate or severe dysplasia, in which the ratio of malignant transformation was higher than in the cases with simple epithelial hyperplasia (P < 0.005). Clinical parameters associated with an increased risk of malignant transformation were female gender and epithelial dysplasia was more often seen in non-homogenous leukoplakias than in homogenous (P < 0.005).

CONCLUSIONSNon-dysplastic leukoplakia may become malignant. Epithelial dysplasia was associated with an increased risk of malignant transformation. Leukoplakia in female may be at a higher risk for malignant transformation.

Adult ; Aged ; Cell Transformation, Neoplastic ; Female ; Humans ; Hyperplasia ; Leukoplakia, Oral ; pathology ; Male ; Middle Aged ; Mouth Mucosa ; pathology ; Mouth Neoplasms ; pathology ; Precancerous Conditions ; pathology ; Retrospective Studies ; Risk Factors ; Sex Factors