Langerhans cell histiocytosis (LCH) is a rare hematological disorder characterized by local or generalized, uncontrolled proliferation and infiltration of Langerhans type of histiocytic cells. It represents a spectrum of clinicopathologic... more
Langerhans cell histiocytosis (LCH) is a rare hematological disorder characterized by local or generalized, uncontrolled proliferation and infiltration of Langerhans type of histiocytic cells. It represents a spectrum of clinicopathologic disorders, ranging from a highly aggressive and frequently fatal multisystem disease to an easily cured solitary lesion of bone. Involvement of children and the younger age group is more common than the adults. Oral cavity involvement occurs early in LCH, but the initial symptoms are generally nonspecific, often causing misdiagnosis. This report describes a rare case of chronic localized LCH in an adult patient, with involvement of oral cavity. A 34-year-old male patient presented with multiple nodulo-papular, ulcerated lesions in gingiva involving both the jaws (primarily mandible) and the left buccal mucosa, in addition to regional teeth mobility. The most striking feature was that even after extraction of mobile teeth, the lesions persisted. After recording proper history, performing clinical and radiological evaluation, an incisional biopsy was performed followed by histopathology and immunohistochemistry to reach a confirmatory diagnosis of LCH, thereby implementing early and appropriate initiation of treatment.
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The effect of iron and steel slag and fly ash additions on the physicomechanical properties, phase, and microstructure of normal porcelain compositions replacing quartz in full and feldspar in part was investigated. Two compositions,... more
The effect of iron and steel slag and fly ash additions on the physicomechanical properties, phase, and microstructure of normal porcelain compositions replacing quartz in full and feldspar in part was investigated. Two compositions, varying the amount of slag and fly ash, were prepared and the compacts made out of them were heated in the temperature range of 1100–1180 °C. Both porous and vitrified samples were obtained. The samples heated at 1150 C resulted in 7–9 % water absorption, lower shrinkage (56 %) and superior flexural strength (50–58 MPa) from both compositions. The highly porous sample heated at 1100 °C resulted in 16–18 % water absorption, around 40 MPa flexural strength and shrinkage in the range of 2–3 %. It was interesting to observe that the vitrified samples offered lower flexural strength (40–50 MPa) than the porous samples heated at 1150 °C. These properties were correlated with phase and microstructural observations. Anorthite crystals were present as a major phase in both and the microstructure was highly crystalline.
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Research Interests:
Calcifying epithelial odontogenic tumor (CEOT), also known as Pindborg tumor, is a rare benign but locally aggressive odontogenic neoplasm, accounts for <1% of all odontogenic tumors. CEOT is usually seen in the posterior area of the... more
Calcifying epithelial odontogenic tumor (CEOT), also known as Pindborg tumor, is a rare benign but locally aggressive odontogenic neoplasm, accounts for <1% of all odontogenic tumors. CEOT is usually seen in the posterior area of the mandible in-between 30 and 50 years of age without definite sex predilection. A painless, slow-growing swelling with bone expansion is the most common clinical feature of CEOT. Radiographically, it presents as a mixed radiographic lesion may or may not be associated with any impacted tooth. Confirmation of the diagnosis is made by histopathological examination. The tumor has a recurrence rate of 10%–20% and so periodic follow-up is necessary. A unique case of CEOT involving the right mandibular molar–premolar in a 25-year-old female patient with clinical behavior, radiological, histopathological features and surgical managements is discussed herewith.
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Diagnostic ambiguities regarding the malignant potentiality of oral submucous fibrosis (OSF), an oral precancerous condition having dysplastic and non-dysplastic isoforms are the major failure for early intervention of oral squamous cell... more
Diagnostic ambiguities regarding the malignant potentiality of oral submucous fibrosis (OSF), an oral precancerous condition having dysplastic and non-dysplastic isoforms are the major failure for early intervention of oral squamous cell carcinoma (OSCC) patients. Our goal is to identify proteomic signatures from biopsies that can be used as precancer diagnostic marker for patient suffering from OSF. The high throughput techniques adopting de novo peptide sequencing (1D SDS-PAGE coupled nanoLC MALDI tandem mass spectrometry (MS/MS)-based peptide mass fingerprint), immunohistochemistry (IHC), Western blot (WB) and real-time PCR (RT-PCR) analysis are considered for such biomarker identification and multilevel validations. Alpha-enolase is identified as an overexpressed protein in biopsies of oral submucous fibrosis with dysplasia (OSFWD) compared with oral submucous fibrosis without dysplasia (OSFWT) and normal oral mucosa (NOM). Total proteome analysis of an overexpressed protein band around 47 kDa of OSFWD identifies 334 peptides corresponding to 61 human proteins. Among them α-enolase is identified as a prime protein with highest number of peptides (44 out of 334 peptides) and sequence coverage (66.4%). Furthermore, RT-PCR, WB and IHC analysis also show mRNA and tissue level upregulation of α-enolase in OSFWD validating α-enolase as precancer marker. This study for the first time identifies and validates α-enolase as a novel biomarker for early diagnosis of malignant potentiality of OSF. Hence, the identified protein marker, α-enolase can help in early therapeutic intervention of OSF patients leading to the reduction of patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s pain, treatment cost and enhancement of patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s quality of life.
Research Interests: Quality of life, Proteomics, Immunohistochemistry, Adolescent, Medicine, and 15 moreClinical Pathology, Biopsy, Humans, Female, Oral submucous fibrosis, Male, Clinical Sciences, Biomarker, Precancerous Conditions, Adult, Mouth mucosa, Prognosis, Enolase, Early Diagnosis, and real time polymerase chain reaction
The effect of Cr-doped soda-lime scrap glass in normal porcelain composition substituting feldspar partially on their physico-mechanical properties such as % linear shrinkage, % apparent porosity, bulk density and flexural strength were... more
The effect of Cr-doped soda-lime scrap glass in normal porcelain composition substituting feldspar partially on their physico-mechanical properties such as % linear shrinkage, % apparent porosity, bulk density and flexural strength were studied in the temeprature range of 1100C to 1250C and the data was compared with normal porcelain composition. It was observed that incorporation of Cr-doped soda-lime scrap glass in place of feldspar enhances the vitrification and develop higher flexural strength. The phase and microstructural evolution were analysed by XRD and FESEM studies. The porcelain with Cr-doped soda-lime silica glass shows formation of needle shaped mullite crystals. No significant change in crystal morphology was noted when compared with normal porcelain sdudied earlier by the same authors. However presence of large no of smaller sized mullite crystals are seen in the presently developed scrap glass incorporated porcelain composition.
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Oral leukoplakia (OLK) is the most common pre malignant disorder (PMD) with highest malignant potentiality. It is clinically highly correlated with oral squamous cell carcinoma (OSCC). Painful biopsy is the gold standard till date for... more
Oral leukoplakia (OLK) is the most common pre malignant disorder (PMD) with highest malignant potentiality. It is clinically highly correlated with oral squamous cell carcinoma (OSCC). Painful biopsy is the gold standard till date for diagnosis of these diseases. Again for specific grading of such pathological states and mitigation of inter and intra observer variability and subjective disease classification, alternative of molecular biomarkers for diseases differentiation as well as non-invasive modalities are yet to be explored. In this study role of morphometric, intensity and textural features extracted from liquid based exfoliative cytology (LBEC) and intensity and textural features extracted from ex vivo optical coherence tomography (OCT) images and spectral features from difference between mean spectra (DBMS) were evaluated for disease classification using variants of support vector machine (SVM) classifiers. Result showed that at 10 fold cross-validation OLK and OSCC could be differentiated using cellular features of LBEC data at 100% sensitivity and specificity. Spectral biomarkers were also extracted efficiently which could classify the diseases with 81.3% sensitivity and 91.3% specificity depicting role of chemical molecules responsible in pathological alteration. Considering the advantage of each modality, it can be concluded that these features can utilized as disease differentiation markers and have useful clinical implication for diagnosis of OLK and OSCC towards mitigation of inter- as well as intra observer variability faced during routine histopathological diagnostic procedure.
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Oral leukoplakia (OLK) is the most common pre malignant disorder (PMD) with highest malignant potentiality. It is clinically highly correlated with oral squamous cell carcinoma (OSCC). Painful biopsy is the gold standard till date for... more
Oral leukoplakia (OLK) is the most common pre malignant disorder (PMD) with highest malignant potentiality. It is clinically highly correlated with oral squamous cell carcinoma (OSCC). Painful biopsy is the gold standard till date for diagnosis of these diseases. Again for specific grading of such pathological states and mitigation of inter and intra observer variability and subjective disease classification, alternative of molecular biomarkers for diseases differentiation as well as non-invasive modalities are yet to be explored. In this study role of morphometric, intensity and textural features extracted from liquid based exfoliative cytology (LBEC) and intensity and textural features extracted from ex vivo optical coherence tomography (OCT) images and spectral features from difference between mean spectra (DBMS) were evaluated for disease classification using variants of support vector machine (SVM) classifiers. Result showed that at 10 fold cross-validation OLK and OSCC could be differentiated using cellular features of LBEC data at 100% sensitivity and specificity. Spectral biomarkers were also extracted efficiently which could classify the diseases with 81.3% sensitivity and 91.3% specificity depicting role of chemical molecules responsible in pathological alteration. Considering the advantage of each modality, it can be concluded that these features can utilized as disease differentiation markers and have useful clinical implication for diagnosis of OLK and OSCC towards mitigation of inter- as well as intra observer variability faced during routine histopathological diagnostic procedure.
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Diagnosis of oral cancer using pathology is becoming more dependent on digital imaging. Since precancerous conditions like Oral submucous fibrosis originate in the basal layer of the tissue, it is very important to investigate the cell... more
Diagnosis of oral cancer using pathology is becoming more dependent on digital imaging. Since precancerous conditions like Oral submucous fibrosis originate in the basal layer of the tissue, it is very important to investigate the cell nuclei of the basal layer in Haematoxylin and Eosin stained tissue as it contains diagnostically important information. For that, accurate identification and segmentation of the nuclei is imperative. Our algorithm uses differential contrast enhancement and distance map transformations to segment out the cell nuclei in ImageJ Software. The algorithm performed successfully on high magnification images with high speed and relative simplicity thus proving its credibility. The nuclear attributes like entropy, polarity, and compactness are calculated and the values obtained are then statistically analyzed using Mann-Whitney U Test using SPSS Software to differentiate between normal and OSF(with severe dysplasia and without dysplasia). The results showed that in case of entropy, statistical significant difference $(\mathbf{p} < \pmb{0.0001})$ is present between all the above mentioned three classes but in cases of compactness and polarity, statistical significant differences are present between normal and diseased classes, but not between OSF (without dysplasia) and OSF (with severe dysplasia) cases for both attributes $(\mathbf{p}=\pmb{0.1527}$ for compactness and $\mathbf{p}\pmb{=0.6965}$ for polarity).
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After the first observations of life under the microscope, it took almost two centuries of research before the idea that all living things are composed of cells or their products was speculated. The development of the microscope was a... more
After the first observations of life under the microscope, it took almost two centuries of research before the idea that all living things are composed of cells or their products was speculated. The development of the microscope was a requirement for the discovery of cells. In 1673, the Dutch botanist, Anton van Leeuwenhoek, reported seeing a myriad of microscopic "animalcules" in water. Over several decades, knowledge about the structure and functions of the cell has progressed tremendously due to the advancement in various techniques like next generation sequencing, and genome wide analysis. Cancers are generated from normal cells by random karyotypic rearrangements. Immortality is a common characteristic of cancers, but its origin and purpose are still unclear. Since such rearrangements disturb long-established mitosis genes, cancer karyotypes vary instinctively but are stabilized perpetually by clonal selections for autonomy. The differentiation stage of tumors is a vi...
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Rhabdomyosarcoma (RMS) is a rare, rapidly growing, highly aggressive malignant neoplasm, originating from undifferentiated mesenchymal cells that retain their ability to differentiate into skeletal muscle. It mainly affects children,... more
Rhabdomyosarcoma (RMS) is a rare, rapidly growing, highly aggressive malignant neoplasm, originating from undifferentiated mesenchymal cells that retain their ability to differentiate into skeletal muscle. It mainly affects children, accounts for <1% of all adult malignancies and has varied clinical presentations. The head and neck region accounts for 35%–40% of all RMS cases, of which 10%–12% cases involve the oral cavity. This report deals with a case of RMS in a 40-year-old woman, primarily involving maxillary gingiva for which she underwent excision with subsequent recurrences. The uniqueness of this case is that it reminds us of the essential clinical dictum that ‘every growth we encounter, no matter how benign it appears clinically, should be looked upon with suspicion’. Hence, proper integration of history, clinical examination and investigation is required to reach a correct diagnosis enabling early treatment, thereby preventing functional and aesthetic loss and psycholog...
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Knowledge of biological and mechanical properties of native tissues is critical for biomaterial design and synthesis for tissue engineering. So far, selection of biomaterials for dental pulp regeneration has been done randomly or based on... more
Knowledge of biological and mechanical properties of native tissues is critical for biomaterial design and synthesis for tissue engineering. So far, selection of biomaterials for dental pulp regeneration has been done randomly or based on experience mainly due to the scarcity of data of biomechanical properties of human dental pulp tissue. This study, for the rst time, characterizes the physical properties of human dental pulp tissue harvested from wisdom teeth, under compression and compared it with PRF and a novel crosslinked PRF (C-PRF) prepared by crosslinking PRF with tannic acid. The results revealed that conventional PRF compressive sterength is very less compared to dental pulp tissue and comparable compressive strength of the novel crosslinked PRF(C-PRF). Taken collectively, crosslinked PRF will better suit for pulp tissue engineering purposes.
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The biology is disrupted for many reasons which are sometimes fathomable and sometimes not. The paramount factors can be genetic and variations acquired but both subsequently gives the catastrophic outcome in case of menacing disease such... more
The biology is disrupted for many reasons which are sometimes fathomable and sometimes not. The paramount factors can be genetic and variations acquired but both subsequently gives the catastrophic outcome in case of menacing disease such as cancer. The detection of it has been done and goes way back but newer technology is taking over every decade in order to make it more and more precise. As human intervention can lead to errors, automated detection can improve the accuracy. Therefore in this study, convolutional neural network (CNN) has been explored for detection of normal and different stages of oral submucous fibrosis from microscopic images of stained biopsy samples. Data pre-processing has been implemented before feeding the images into neural network and an overall accuracy of 99.4% has been achieved which shows the effectiveness of CNN for the same.
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Saliva has emerged as an efficient screening sample for early stage detection of oral cancer (OC) owing to non-invasiveness coupled with high sensitivity and specificity. Although spectroscopic characterization of saliva in oral... more
Saliva has emerged as an efficient screening sample for early stage detection of oral cancer (OC) owing to non-invasiveness coupled with high sensitivity and specificity. Although spectroscopic characterization of saliva in oral potentially malignant disorders OPMDs) and OC is extensively studied, its potential as imaging biomarker is sparsely explored. Further, the literature on crystalline pattern of saliva for other diseases or different physiological conditions is mostly qualitative. This paper proposed multifractal based methodology to quantitatively study alteration of the salivary fern pattern in different OPMDs and OC in relation to normal counterpart. The fern pattern of dried saliva is captured by stereo-zoom microscope in reflective mode and an image dataset is developed. We resort to two dimensional multi-fractal detrended fluctuation analysis (2d MFDFA) to elucidate the complexity and heterogeneity of these micro-structured patterns. Existence of multifractal nature embedded in salivary fern has been validated for the first time. Long range spatial correlation is found to be the origin of multifractality. Variation in multi-scale self-similarity of irregular pattern in different study groups is demonstrated by four features extracted from MFDFA. Statistical analysis shows discriminating nature of these features for combinations of pairwise interclass classification. This study sheds light on acceptability of microscopic images of arborized saliva in fast and cost effective screening of different oral lesions.
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Significance Existing procedures of screening subsurface cancers are either prohibitively resource-intensive and expensive or are unable to provide direct quantitative estimates of the relevant physiological parameters for accurate... more
Significance Existing procedures of screening subsurface cancers are either prohibitively resource-intensive and expensive or are unable to provide direct quantitative estimates of the relevant physiological parameters for accurate classification accommodating interpatient variabilities and overlapping clinical manifestations. Here, we introduce a handheld and inexpensive blood perfusion imager that provides a noninvasive in situ screening approach for distinguishing precancer, cancer, and normal scenarios by precise quantitative estimation of the localized blood circulation in the tissue over an unrestricted region of interest without any unwarranted noise in the data, augmented by machine learning–based classification. Clinical trials in minimally resourced settings have established the efficacy of the method in differentiating cancerous and precancerous stages of suspected oral abnormalities, as verified by gold-standard biopsy reports.
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Research Interests:
Fibrosis is an extracellular matrix disease affecting several vital organs' functions and can lead to life-threatening pathologies like cancer. The standard diagnostic protocol involves an immuno-histochemical examination of the... more
Fibrosis is an extracellular matrix disease affecting several vital organs' functions and can lead to life-threatening pathologies like cancer. The standard diagnostic protocol involves an immuno-histochemical examination of the fibrosis-linked protein's distribution in the tissues. Of specific interest are the primarily affected dense matrix-proteins like collagen. But labeling such dense proteins is prone to subjectivity. Besides distribution, the collagen nano-fibril characteristics, usually revealed by ultra-structural imaging, also have diagnostic relevance. Super-resolution microscopy can aid high-resolution clinical decisions by imaging protein nano-structures but is challenging for dense proteins. Here we exploit the natural fluctuations of tissue autofluorescence (tAF) signal from proteins in dense tissue matrix for super-resolving them. We achieved super-resolution over a clinically relevant large area using a simple, low-cost, low numerical aperture (NA) optical m...
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The effect of Cr-doped soda-lime scrap glass in normal porcelain composition substituting feldspar partially on their physico-mechanical properties such as % linear shrinkage, % apparent porosity, bulk density and flexural strength were... more
The effect of Cr-doped soda-lime scrap glass in normal porcelain composition substituting feldspar partially on their physico-mechanical properties such as % linear shrinkage, % apparent porosity, bulk density and flexural strength were studied in the temeprature range of 1100C to 1250C and the data was compared with normal porcelain composition. It was observed that incorporation of Cr-doped soda-lime scrap glass in place of feldspar enhances the vitrification and develop higher flexural strength. The phase and microstructural evolution were analysed by XRD and FESEM studies. The porcelain with Cr-doped soda-lime silica glass shows formation of needle shaped mullite crystals. No significant change in crystal morphology was noted when compared with normal porcelain sdudied earlier by the same authors. However presence of large no of smaller sized mullite crystals are seen in the presently developed scrap glass incorporated porcelain composition.
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Calcifying cystic odontogenic tumor (CCOT) is a rare odontogenic lesion comprising about 2% of all odontogenic pathological changes in the jaw. Clinically presents as painless swelling of jaw, while histopathology demonstrates... more
Calcifying cystic odontogenic tumor (CCOT) is a rare odontogenic lesion comprising about 2% of all odontogenic pathological changes in the jaw. Clinically presents as painless swelling of jaw, while histopathology demonstrates characteristic "Ghost" epithelial cells with a propensity to calcify. Due to its varied clinical presentation, including cystic and neoplastic forms and recurrence rates posses a great challenge to decide its course of treatment. Here, we report, a classic case of CCOT, showing an aggressive clinical course and different histopathologic presentations along with a brief review of literature.
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The effect of iron and steel slag and fly ash additions on the physicomechanical properties, phase, and microstructure of normal porcelain compositions replacing quartz in full and feldspar in part was investigated. Two compositions,... more
The effect of iron and steel slag and fly ash additions on the physicomechanical properties, phase, and microstructure of normal porcelain compositions replacing quartz in full and feldspar in part was investigated. Two compositions, varying the amount of slag and fly ash, were prepared and the compacts made out of them were heated in the temperature range of 1100–1180 °C. Both porous and vitrified samples were obtained. The samples heated at 1150 C resulted in 7–9 % water absorption, lower shrinkage (56 %) and superior flexural strength (50–58 MPa) from both compositions. The highly porous sample heated at 1100 °C resulted in 16–18 % water absorption, around 40 MPa flexural strength and shrinkage in the range of 2–3 %. It was interesting to observe that the vitrified samples offered lower flexural strength (40–50 MPa) than the porous samples heated at 1150 °C. These properties were correlated with phase and microstructural observations. Anorthite crystals were present as a major ph...
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Dear Editor, Oral cancer is the 11th most common cancer in the world and, considering deaths, it ranks sixth worldwide as per reports by International Agency for Research on Cancer. The majority of patients are in developing countries,... more
Dear Editor, Oral cancer is the 11th most common cancer in the world and, considering deaths, it ranks sixth worldwide as per reports by International Agency for Research on Cancer. The majority of patients are in developing countries, with the highest prevalence of up to 40% reported in the Indian subcontinent. It has been shown that 80% of the oral cancers found in the Indian subcontinent develop from pre-existing pre-malignant oral lesions. Oral submucous fibrosis (OSF) is the most common precancerous condition because of the habit of chewing areca nut, tobacco along with lime and various concoctions. There is a need for early detection of the malignant potentiality that is present in premalignant conditions so that the disease can be diagnosed at its earliest and managed better. There is no specific treatment for OSF so far and the diagnosis is based on interpretation of haematoxylin and eosin-stained histopathological sections, which is a 100-year-old method and considered as a...
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ABSTRACT: Verrucous Carcinoma is a slow growing , well demarcated unique variant of Oral Squamous Cell Carcinoma (OSCC) with a characteristic histopathological presentation. It is a rare tumor which is well known for its local... more
ABSTRACT: Verrucous Carcinoma is a slow growing , well demarcated unique variant of Oral Squamous Cell Carcinoma (OSCC) with a characteristic histopathological presentation. It is a rare tumor which is well known for its local aggressiveness and minimal metastatic potential. The disease should be exclusively studied on the ground of its non carcinomatous nature and differentiated from OSCC. Here we report two cases of Verrucous Carcinoma involving the buccal mucosa along with a thorough review of scientific literature. KEYWORDS: Verrucous Carcinoma, Papillary Projections, Bulbous rete pegs, Parakeratin plugging
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The choice of tissue fixation is critical for preserving the morphology and biochemical information of tissues. Fragile oral tissues with lower tensile strength are challenging to process for histological applications as they are prone to... more
The choice of tissue fixation is critical for preserving the morphology and biochemical information of tissues. Fragile oral tissues with lower tensile strength are challenging to process for histological applications as they are prone to processing damage, such as tissue tear, wrinkling, and tissue fall-off from slides. This leads to loss of morphological information and unnecessary delay in experimentation. In this study, we have characterized the new PAXgene tissue fixation system on oral buccal mucosal tissue of cancerous and normal pathology for routine histological and immunohistochemical applications. We aimed to minimize the processing damage of tissues and improve the quality of histological experiments. We also examined the preservation of biomolecules by PAXgene fixation using FTIR microspectroscopy. Our results demonstrate that the PAXgene-fixed tissues showed significantly less tissue fall-off from slides. Hematoxylin and Eosin staining showed comparable morphology betw...
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This paper focuses on the status of epithelial markers, E-cadherin, and p63 in the backdrop of an abnormal amount of collagen in the sub-mucosa of dysplastic and non-dysplastic grades of OSF. Histologically confirmed OSF and normal oral... more
This paper focuses on the status of epithelial markers, E-cadherin, and p63 in the backdrop of an abnormal amount of collagen in the sub-mucosa of dysplastic and non-dysplastic grades of OSF. Histologically confirmed OSF and normal oral mucosa samples were procured. Samples were stained by Van Gieson’s stain (VG) and immunohistochemistry. The captured images were analyzed by ImageJ software to quantify their grayscale intensities. There was a gradual increase in the intensity of VG stain from normal to non-dysplastic and dysplastic OSF and the differences in their mean grayscale values were found to be significant ( p < 0.00001). The intensity of E-cadherin was found to be the highest in non-dysplastic conditions and lowest in dysplastic conditions. The intensity difference of E-cadherin between normal and non-dysplastic OSF was found to be significant ( p < 0.00001). The grayscale scale intensity values for p63 in whole epithelium depicted significant differences between normal and diseased conditions but for its intensity, in basal cells, significant differences were found between non-dysplastic and other classes of tissues. There was a positive correlation observed between VG and p63 staining intensity. The diseased oral epithelium demonstrated greater deposition of sub-epithelial collagen fibers along with subsequent loss of E-cadherin and an increased p63 expression.
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Oral cancer is a leading malignancy and a rising concern in India. Early detection of the disease is essential at reducing mortality. In this paper, we propose a computer assisted method for diagnosis of oral pre-cancer/cancer using oral... more
Oral cancer is a leading malignancy and a rising concern in India. Early detection of the disease is essential at reducing mortality. In this paper, we propose a computer assisted method for diagnosis of oral pre-cancer/cancer using oral exfoliative cytology. A combination of features were extracted from expert delineated cells and nuclei collected from cytology of patients suffering from oral sub-mucous fibrosis, oral leukoplakia or oral squamous cell carcinoma and subject with no lesion. These features were used to train predictive machine learning models like support vector machine, k nearest neighbor, random forest, etc. These models were verified using validation data set. The verification experiments showed promising results with the random forest classifier having a test accuracy of 90%.
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Abstract The exact process of the malignant conversion of oral submucous fibrosis (OSF) to oral cancer is not fully understood. This study aimed to detect and analyze E-cadherin expression, p63 expression, and number of mitotic figures,... more
Abstract The exact process of the malignant conversion of oral submucous fibrosis (OSF) to oral cancer is not fully understood. This study aimed to detect and analyze E-cadherin expression, p63 expression, and number of mitotic figures, all correlated to cancer development, in ApoTome images of oral tissues to determine the oncogenic potentiality of OSF. ApoTome images of the study groups (6 normal, 16 OSF with dysplasia, and 10 OSF without dysplasia) were recorded. Cytoplasmic and membranous E-cadherin expression, breakages of the cell membrane, and p63 expression were detected in MATLAB 2016b. The number of mitotic figures detected by MATLAB was correlated with the number of chromosomes detected by ImageJ. A Mann–Whitney U test was done to determine a significant difference between the study groups for cytoplasmic and membranous E-cadherin distribution points. Statistical significant differences were found for cytoplasmic E-cadherin distribution between normal and OSF (with dysplasia) (p = 0.0278). There was an increase in mitotic figures, p63 expression, and cytoplasmic E-cadherin expression and a decrease in membranous E-cadherin expression from normal to diseased condition. Hence, automated detection and quantification of E-cadherin, p63, and mitotic figures in ApoTome images of oral biopsies can help in determining the oncogenic potentiality of OSF.
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Oral sub-mucous fibrosis (OSF) is a pathophysiological state of oral cavity or oropharynx having a high chance of conversion to oral squamous cell carcinoma (OSCC). It involves fibrotic transformation of sub-epithelial matrix along with... more
Oral sub-mucous fibrosis (OSF) is a pathophysiological state of oral cavity or oropharynx having a high chance of conversion to oral squamous cell carcinoma (OSCC). It involves fibrotic transformation of sub-epithelial matrix along with epithelial abnormalities. The present work aims to unveil the mechanistic domain regarding OSF to OSCC conversion exploring the scenario of hypoxia associated oxidative stress, epithelial-mesenchymal transition (EMT), metastasis and stemness acquisition. The study involves histopathological analysis of the diseased condition along with the exploration of oxidative stress status, assessment of mitochondrial condition, immunohistochemical analysis of HIF-1α, E-cadherin, vimentin, ERK, ALDH-1, CD133, Shh, Gli-1 and survivin expressions in the oral epithelial region together with the quantitative approach towards collagen deposition in the sub-epithelial matrix. Oxidative stress was found to be associated with type-II EMT in case of OSF attributing the development of sub-epithelial fibrosis and type-III EMT in case of OSCC favoring malignancy associated metastasis. Moreover, the acquisition of stemness during OSCC can also be correlated with EMT. Alteration of Shh and Gli-1 expression pattern revealed the mechanistic association of hypoxia with the phenotypic plasticity and disease manifestation in case of OSF as well as OSCC. Shh/ Gli-1 signaling can also be correlated with survivin mediated cytoprotective phenomenon under oxidative stress. Overall, the study established the correlative network of hypoxia associated oxidative stress, EMT and manifestation of oral pre-cancerous and cancerous condition in a holistic approach that may throw rays of hope in the therapeutic domain of the concerned diseases.
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Pleomorphic Adenoma (PA), a benign neoplasm of glandular origin most commonly involves major salivary glands. It is rare in minor salivary glands such as hard palate, upper lip and buccal mucosa, frequently affecting middle aged females.... more
Pleomorphic Adenoma (PA), a benign neoplasm of glandular origin most commonly involves major salivary glands. It is rare in minor salivary glands such as hard palate, upper lip and buccal mucosa, frequently affecting middle aged females. PA comprises diverse histopathologic features of epithelial, myoepithelial and mesenchymal components. Aberrant histopathologic features in Pleomorhic Adenoma thus calls for judicious discrimination from alike entities which facilitates appropriate surgical management. Here we present a case report of PA in upper lip in a 25 year old female patient showing uncommon findings like clear cells, squamous metaplasia and cribriform pattern.
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Bright-field microscopy (BFM) encrypts the optical transillumination profile of the transmitted light attenuated by the complex micro-structural tissue convolutions, manifested by the dense and compact regions of the specimen under... more
Bright-field microscopy (BFM) encrypts the optical transillumination profile of the transmitted light attenuated by the complex micro-structural tissue convolutions, manifested by the dense and compact regions of the specimen under examination. The connotations of idiosyncratic tissue interaction dynamics with the onset of pre-cancerous activity are encoded in the BFM acquired oral mucosa histopathological images (OMHI). In the present study, our analysis is focused on the sub-epithelium region of the oral mucosa, which has high clinical significance but sparsely explored in the literature from the textural domain. Histopathology being the gold-standard technique till date, we have used the light microscopic histopathology images for tissue characterization. The tissue-index transmission patches (TITP) from the sub-epithelium region are cropped under the guidance of oral onco-pathologists. After that, the TITPs are characterized for its multi-scale spatial-deformation dynamics, while keeping the intrinsic anisotropic geometry, and local contour connectivity within tolerable limits. With recent studies exhibiting multifractal's potency in diverse biological system analysis, here, we exploit the 2D multifractal detrended fluctuation analysis (2D-MFDFA) on TITPs for exploring a discriminative set of multifractal signatures for healthy, oral potentially malignant disorders and oral cancer tissue sample. The predictive model's competency is validated on an experimentally collected corpus of TITP samples and substantiated via confirmatory data statistics and analysis, showing its inter-class segregation efficacy. Moreover, the 2D-MFDFA analysis evinces the complex multifractal patterns in TITPs, which is due to the presence of composite long-range correlations in the oral mucosa tissue fabric.
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Background: In the context of early diagnosis and prevention of oral cancer, precise assessment of malignant potentiality of the oral potentially malignant disorders, particularly oral submucous fibrosis (OSF) is crucial. Till date, the... more
Background: In the context of early diagnosis and prevention of oral cancer, precise assessment of malignant potentiality of the oral potentially malignant disorders, particularly oral submucous fibrosis (OSF) is crucial. Till date, the assessment of malignant potentiality suffers from predictive ambiguity due to the lack of precision in the gold standard techniques. This can be addressed by integrating heuristic domain knowledge with quantitative analysis. Aim: The aim of this study is to propose an index for enhancing accuracy in malignant potentiality evaluation. Materials and Methods: The present study analyzes important histomorphometric attributes (epithelial thickness, basal cell nuclear size, nuclear-to-cytoplasmic area ratio of basal cells, chromaticity of basal cell nucleus, thickness of basement membrane, ratio of vasculature in juxta-epithelial connective tissue [i.e., area covered by blood vessels/total area], collagen density in the lamina propria) of oral mucosa in dysplastic and nondysplastic OSF in association with relevant oncopathological appreciations (weightage of different features as suggested by oral pathologists) toward proposing a “Malignant Potentiality Index” (MPI). Results: Analysis of variance and notch box plot analysis depict statistically significant differences (P < 0.0001) in the histopathological features among different study groups (normal oral mucosa, OSF without dysplasia, OSF with dysplasia). Histopathological observation of one OSF patient with calculated MPI is shown. Conclusion: This newly proposed diagnostic cum prognostic decision-making parameter, the “MPI” may bring a value addition to the conventional diagnostic gold standard.
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Background: Saliva based diagnostic can play an important role in the translational research related to cancer diagnostics and treatment. It is easily available, noninvasive, low storage cost, has less contamination chances with simple... more
Background: Saliva based diagnostic can play an important role in the translational research related to cancer diagnostics and treatment. It is easily available, noninvasive, low storage cost, has less contamination chances with simple collection procedure. Cancers related to tobacco use, including oral cancer account for about 30% of all cancers in males and females. Five…
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Langerhans cell histiocytosis (LCH) is a rare hematological disorder characterized by local or generalized, uncontrolled proliferation and infiltration of Langerhans type of histiocytic cells. It represents a spectrum of clinicopathologic... more
Langerhans cell histiocytosis (LCH) is a rare hematological disorder characterized by local or generalized, uncontrolled proliferation and infiltration of Langerhans type of histiocytic cells. It represents a spectrum of clinicopathologic disorders, ranging from a highly aggressive and frequently fatal multisystem disease to an easily cured solitary lesion of bone. Involvement of children and the younger age group is more common than the adults. Oral cavity involvement occurs early in LCH, but the initial symptoms are generally nonspecific, often causing misdiagnosis. This report describes a rare case of chronic localized LCH in an adult patient, with involvement of oral cavity. A 34-year-old male patient presented with multiple nodulo-papular, ulcerated lesions in gingiva involving both the jaws (primarily mandible) and the left buccal mucosa, in addition to regional teeth mobility. The most striking feature was that even after extraction of mobile teeth, the lesions persisted. After recording proper history, performing clinical and radiological evaluation, an incisional biopsy was performed followed by histopathology and immunohistochemistry to reach a confirmatory diagnosis of LCH, thereby implementing early and appropriate initiation of treatment.
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Computational analysis on altered micro-nano-textural attributes of the oral mucosa may provide precise diagnostic information about oral potentially malignant disorders (OPMDs) instead of an existing handful of qualitative reports. This... more
Computational analysis on altered micro-nano-textural attributes of the oral mucosa may provide precise diagnostic information about oral potentially malignant disorders (OPMDs) instead of an existing handful of qualitative reports. This study evaluated micro-nano-textural features of oral epithelium from scanning electron microscopic (SEM) images and the sub-epithelial connective tissue from light microscopic (LM) and atomic force microscopic (AFM) images for normal and OPMD (namely oral sub-mucous fibrosis, i.e., OSF). Objective textural descriptors, namely discrete wavelet transform, gray-level co-occurrence matrix (GLCM), and local binary pattern (LBP), were extracted and fed to standard classifiers. Best classification accuracy of 87.28 and 93.21%; sensitivity of 93 and 96%; specificity of 80 and 91% were achieved, respectively, for SEM and AFM. In the study groups, SEM analysis showed a significant (p < 0.01) variation for all the considered textural descriptors, while for ...
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Abnormal epithelial stratification is a sign of oral dysplasia and hence evaluation of surface characteristics of oral epithelial region can help in detection of cancerous progression. Surface characteristics can be better visualised by... more
Abnormal epithelial stratification is a sign of oral dysplasia and hence evaluation of surface characteristics of oral epithelial region can help in detection of cancerous progression. Surface characteristics can be better visualised by Scanning Electron Microscopy (SEM) in comparison to light microscopy. In our study we have developed automated image processing algorithms i.e. Gaussian with median filtering and Gradient filtering, using MATLAB 2016b, to segment the surface characteristics i.e. the ridges and pits in the SEM images of oral tissue of normal (13 samples) and Oral Submucous Fibrosis (OSF) (36 samples) subjects. After segmentation, quantitative measurement of the parameters like area, thickness and textural features like entropy, contrast and range filter of ridges as well as area of pit and the ratio of area of ridge vs. area of pit was done. Statistical significant differences were obtained in between normal and OSF study groups for thickness (p=0.0107), entropy (p<0.00001) and contrast of ridge (p<0.00001) for Gaussian with median filtering and for all the parameters except thickness of the ridge(p=1.386), for Gradient filtering. Thus, computer aided image processing by Gradient filter followed by quantitative measurement of the surface characteristics provided precise differentiation between normal and precancerous oral condition.
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Aim: The methylome associated with miRNA loci was investigated in oral cancer to explore tobacco specific methylation and potential biomarkers for patient survival. Methods: Methylome data was generated from 16 pairs of cancer-normal... more
Aim: The methylome associated with miRNA loci was investigated in oral cancer to explore tobacco specific methylation and potential biomarkers for patient survival. Methods: Methylome data was generated from 16 pairs of cancer-normal tissues by reduced representation bisulfite sequencing method. Differentially methylated regions were identified using the DMAP pipeline. In silico validation and Kaplan–Meier survival analyses were performed on The Cancer Genome Atlas data based on our miRNA methylome data. Results: A total of 4310 unique differentially methylated regions, mapping to 144 miRNA loci, were identified. Three distinct groups of miRNAs were differentially methylated in cancer tissues from smokers, chewers and mixed habitués. Hypermethylation of miR-503, miR-200a/b, miR-320b and miR-489 was associated with worse 5-year survival. Conclusion: Differential methylation patterns in miRNA loci are associated with poor survival underscoring their potential as predictive and prognos...
Research Interests: MicroRNA, Cancer, Biology, Epigenetics, Medicine, and 3 moreEpigenomics, Methylation, and DNA methylation
Epithelial abnormality during the transformation of oral submucous fibrosis (OSF) into oral squamous cell carcinoma has been well studied and documented. However, the differential contribution of atrophy and hyperplasia for malignant... more
Epithelial abnormality during the transformation of oral submucous fibrosis (OSF) into oral squamous cell carcinoma has been well studied and documented. However, the differential contribution of atrophy and hyperplasia for malignant potentiality of OSF is yet to be resolved. Existing diagnostic conjectures lack precise diagnostic attributes which may be effectively resolved by substantiation of specific molecular pathology signatures. Present study elucidates existence of cellular competitiveness in OSF conditions using computer-assisted neighbourhood analysis in quantitative immunohistochemistry (IHC) framework. The concept of field cancerization was contributory in finding correspondence among neighbouring cells of epithelial layers with reference to differential expression of cardinal cancer-related genes [c-Myc (oncogene), p53 (tumour suppressor), and HIF-1α (hypoxia regulator)] which are known to be important sensors in recognizing cellular competitive interface. Our analyses ...