Clinical diagnosis of viral hepatitis: Current status and future strategies.

Viral hepatitis (VH) is a significant public health issue with tremendous potential to aggravate into chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Recent decade has witnessed remarkable uprising in the drug development and effective treatment of VH. An upsurge is seen in identification of antiviral therapies with low rates of viral resistance, the improvement of Hepatitis B Virus (HBV) vaccination and the development of direct-acting antivirals for Hepatitis C Virus (HCV). But unfortunately, the "2030 worldwide eradication" objective of World Health Organization (WHO) is still unmet. It can be largely attributed to the deficit faced by the healthcare system concerning screening and diagnosis. A timely, accurate and comprehensive screening; encompassing maximum population coverage is essential to combat this disease. However, advancements in VH diagnostics remain inadequate and with a marginal use in routine practice. This paper deliberates upon the lacunae in traditional and prevailing diagnostic methodology of viral hepatitis, especially their inadequacy in meeting the unique situations prevailing low- and middle-income countries (LMIC).

The repertoire of mutational signatures in tobacco- and non-tobacco-induced oral cancer

The use of tobacco products is one of the established contributors toward the development and spread of oral cancer. Additionally, recent research has indicated oral microbiome, infections with Human papilloma virus (HPV), Epstein–Barr virus (EBV), Candida as significant contributing factors to this disease along with lifestyle habits. Deregulation of cellular pathways envisaging metabolism, transcription, translation, and epigenetics caused by these risk factors either individually or in unison is manifold, resulting in the increased risk of oral cancer. Globally, this cancer continues to exist as one of the major causes of cancer-related mortalities; the numbers in the developing South Asian countries clearly indicate yearly escalation. This review encompasses the variety of genetic modifications, including adduct formation, mutation (duplication, deletion, and translocation), and epigenetic changes evident in oral squamous cell carcinoma (OSCC). In addition, it highlights the interference caused by tobacco products in Wnt signaling, PI3K/Akt/mTOR, JAK-STAT, and other important pathways. The information provided also ensures a comprehensive and critical revisit to non-tobacco-induced OSCC. Extensive literature survey and analysis has been conducted to generate the chromosome maps specifically highlighting OSCC-related mutations with the potential to act as spectacles for the early diagnosis and targeted treatment of this disease cancer (AU)

The repertoire of mutational signatures in tobacco- and non-tobacco-induced oral cancer.

The use of tobacco products is one of the established contributors toward the development and spread of oral cancer. Additionally, recent research has indicated oral microbiome, infections with Human papilloma virus (HPV), Epstein-Barr virus (EBV), Candida as significant contributing factors to this disease along with lifestyle habits. Deregulation of cellular pathways envisaging metabolism, transcription, translation, and epigenetics caused by these risk factors either individually or in unison is manifold, resulting in the increased risk of oral cancer. Globally, this cancer continues to exist as one of the major causes of cancer-related mortalities; the numbers in the developing South Asian countries clearly indicate yearly escalation. This review encompasses the variety of genetic modifications, including adduct formation, mutation (duplication, deletion, and translocation), and epigenetic changes evident in oral squamous cell carcinoma (OSCC). In addition, it highlights the interference caused by tobacco products in Wnt signaling, PI3K/Akt/mTOR, JAK-STAT, and other important pathways. The information provided also ensures a comprehensive and critical revisit to non-tobacco-induced OSCC. Extensive literature survey and analysis has been conducted to generate the chromosome maps specifically highlighting OSCC-related mutations with the potential to act as spectacles for the early diagnosis and targeted treatment of this disease cancer.

Assessing Long Non-coding RNAs in Tobacco-associated Oral Cancer.

Cancer is one of the compelling and pegged diseases battled by clinicians and researchers worldwide. Among different types of cancer, oral cancer holds the sixth position globally. With an escalating prevalence in Asian countries, India, China, and Pakistan constitute a large proportion of total incidents of oral cancer patients in terms of new cases or deaths. This mounting prevalence is ascribed to poor oral hygiene and rampant use of substances earmarked as potential risk factors for the disease. Risk factors (dietary/lifestyle habits/occupational/environmental) trigger the activation of oncogenes, dysregulation of lncRNA and miRNA, and silence the tumor suppressor genes, which robustly contributes to the onset and progression of tumorigenesis in oral squamous cell carcinoma. Evidence suggests that specific carcinogens identified in tobacco and related products alter many cellular pathways predisposing to advanced stages of oral cancer. Long non-coding RNAs represent a broad group of heterogenous transcripts longer than 200 nucleotides which do not translate to form functional proteins. They regulate various cellular pathways by specifically interacting with other RNAs, DNA, and proteins. Their role in the pathogenesis of OSCC and other cancer is still being debated. In this review, we discuss the molecular insights of significant lncRNAs involved in some crucial deregulated pathways of tobacco-associated OSCC. The implications and challenges to harnessing the potential of lncRNAs as biomarkers in early diagnosis and targeted treatment have also been analyzed.

Rare Carcinoma Ex-pleomorphic Adenoma of Buccal Mucosa: Case Report and Review of Literature.

Carcinoma ex pleomorphic adenoma (CXPA) is exceedingly rare in minor salivary glands of oral cavity. We present a case of CXPA arising from buccal mucosa in a 44-year-old male patient. The man presented to surgery outpatient department with right buccal mucosa swelling. Clinical impression suggests a neoplasm of buccal mucosa and the patient was sent for fine needle aspiration cytology. By examining the cytological smears, possibility of carcinoma was revealed. The mass was dissected and excised with safety margins. Examining Hematoxylin and Eosin slides, final diagnosis of CXPA was given. Patient did not turn for regular follow-ups and presented 1 year after surgery with recurrence at the same site. CXPA is an uncommon malignant tumor with highly aggressive biological behavior. Its occurrence in sites like buccal mucosa is rare. Hence, quite a diagnostic challenge at such sites cause diagnostic difficulties.

Mechanism of gene amplification via yeast autonomously replicating sequences.

The present investigation was aimed at understanding the molecular mechanism of gene amplification. Interplay of fragile sites in promoting gene amplification was also elucidated. The amplification promoting sequences were chosen from the Saccharomyces cerevisiae ARS, 5S rRNA regions of Plantago ovata and P. lagopus, proposed sites of replication pausing at Ste20 gene locus of S. cerevisiae, and the bend DNA sequences within fragile site FRA11A in humans. The gene amplification assays showed that plasmid bearing APS from yeast and human beings led to enhanced protein concentration as compared to the wild type. Both the in silico and in vitro analyses were pointed out at the strong bending potential of these APS. In addition, high mitotic stability and presence of TTTT repeats and SAR amongst these sequences encourage gene amplification. Phylogenetic analysis of S. cerevisiae ARS was also conducted. The combinatorial power of different aspects of APS analyzed in the present investigation was harnessed to reach a consensus about the factors which stimulate gene expression, in presence of these sequences. It was concluded that the mechanism of gene amplification was that AT rich tracts present in fragile sites of yeast serve as binding sites for MAR/SAR and DNA unwinding elements. The DNA protein interactions necessary for ORC activation are facilitated by DNA bending. These specific bindings at ORC promote repeated rounds of DNA replication leading to gene amplification.

Clear cell hidradenoma of breast mimicking atypical breast lesion: a diagnostic pitfall in breast cytology.

Clear cell hidradenoma (CCH) is an uncommon skin adnexal tumor arising from eccrine glands. Although several kind of skin adnexal tumors arise in the breast tissue, CCH of the breast is an extremely rare entity. Failure to identify its cytomorphologic features and rarity of this tumor may lead to misdiagnosis on fine needle aspiration cytology. Hereby we report a case of 30-year-old female who presented with painless lump in left breast since 10 months. Fine needle aspiration cytology of lump yielded fluid material. On May-Grunwald-Giemsa stained smears, a possibility of atypical breast lesion was considered and patient was advised a biopsy examination. Final diagnosis of CCH was made on histopathologic examination. Awareness of cytomorphologic features of breast CCH will prevent misdiagnosis as malignant or atypical breast lesions and will allow for correct management of the patients.

Aggressive angiomyxoma in pregnancy.

Aggressive angiomyxoma (AA) is a rare, slow-growing mesenchymal neoplasm of vulvo-perineal region. Although AA is common in females of reproductive age, only a few cases during pregnancy have been documented in the English literature. It carries a high risk of local recurrence but rarely metastasizes. The high recurrence rate can partially be due to inadequate excision, which may be due to an incorrect preoperative diagnosis. We present a case of 25-year-old pregnant female presenting with a painless and soft mass attached to left labia majora by a stalk. This mass was clinically thought to be a lipoma. It was completely excised and was diagnosed as AA on histopathology. Gynecologists should consider the diagnosis of AA when a young female especially during her pregnancy presents with a vulvo-perineal mass. Incorrect diagnosis may lead to incomplete excision and recurrence.

A cytological study of palpable superficial nodules of parasitic origin: a study of 41 cases.

Background. Few parasitic infestations present as only superficial palpable subcutaneous or intramuscular nodule. The current study highlights the role of FNAC in the diagnosis of superficial palpable parasitic lesions. Methods. This was a retrospective study in which we reviewed the FNAC record of all patients over a period of two years from September 2011 to August 2013. During this period, FNA was performed on 5954 cases which presented as superficial palpable lump at various sites of body. There were 41 cases diagnosed as parasitic lesion or suspicious of parasitic lesion on cytology which were included in the study. Results. In the present study, most of the patients were children and young adults. The lesions were located over trunk in 18 (43.9%) cases, extremities in 12 (29.3%) cases, and head and neck region in 11 (26.8%) cases. Out of 41 cases, 27 (65.8%) cases were confirmed on cytology and/or histopathology as parasitic lesions, including 21 (51.2%) cases of cysticercosis, 5 (12.2%) cases of filariasis, and one (2.4%) case of hydatid cyst. Cytological findings of remaining cases were suggestive of parasitic lesion. Conclusion. Careful assessment of cytological material is helpful to detect parasite or inflammatory response to parasite even in asymptomatic patients.

Primary multilocular hydatid cyst of neck with unique presentation: a rare case report and literature review.

Hydatid cyst (HC) is a parasitic infection caused by larva form of Echinococcus. It occurs frequently in liver and lungs. Primary HC of neck is extremely rare occurrence and here we report it with unusual presentation. A 35-year-old male presented with slowly growing painless swelling in right side of neck for 6-7 years. The swelling measured 11 × 6 cm and cough impulse elicited on local examination. MRI scan revealed a multiloculated cystic lesion in neck. Fine needle aspiration cytology yielded fluid aspirate and smear showed fragment of laminated membrane, suggestive of HC. The intact cyst was removed surgically and histopathologic examination confirmed the diagnosis of HC. Both clinicians and radiologists should consider HC in differential diagnosis of head and neck swelling for proper management.

Histopathological correlation of atypical (c3) and suspicious (c4) categories in fine needle aspiration cytology of the breast.

Introduction. According to the National Cancer Institute (NCI) guidelines in 1996, breast lesions are categorized as C1 to C5 on fine needle aspiration (FNA) cytology. Very few studies are available in the English literature analyzing histopathology outcome of C3 (atypical, probably benign) and C4 (suspicious, probably malignant) lesions. Our study aims to correlate FNA cytology of breast lump diagnosed as C3 and C4 lesion with histopathological examination. Methods. During a period of 2 years, 59 cases of C3 and 26 cases of C4 were retrieved from total 1093 cases of breast FNA. All the cases were reviewed by two cytopathologists independently. The final 24 cases of C3 and 16 cases of C4 categories were correlated with histopathological diagnosis. Result. Among C3 category, 37.5% revealed malignant findings, whereas of C4 category, 87.5% were malignant on histopathology. This difference was statistically significant (P = 0.0017). Sensitivity, specificity, positive predictive values, and negative predictive value of C4 category in diagnosing breast malignancy were 60.8%, 88.2%, 87.5%, and 62.5%, respectively. Conclusion. Although FNAC is simple, safe, cost-effective and accurate method for diagnosis of breast masses, one must be aware of its limitations particularly in C3 and C4 categories. Also, since both these categories carry different probabilities of malignancy and thus different management, we therefore, support maintaining C3 and C4 categories.

Fine-needle aspiration cytology of myoepithelial carcinoma of salivary gland: Diagnostic challenge to cytopathologist.

Myoepithelial carcinoma (MC) is rare malignant salivary gland neoplasm and its cytologic features have been rarely described in the literature. Furthermore, MC shows varied cell types and patterns leading to the wide range of differential diagnosis on cytology. Histopathology and immunohistochemistry (IHC) are necessary to make a definite diagnosis. A 37-year-old female presented with painless, progressive swelling in the infra-auricular region since 2 years. Fine-needle aspiration cytology was performed and cytological possibilities of cellular pleomorphic adenoma and myoepithelial cell neoplasm were rendered and patient was advised excision and histopathologic examination for final diagnosis and subtyping. Final diagnosis of MC was made on hematoxylin and eosin sections and IHC. MC is rare malignant salivary gland tumor showing a clinic-pathologic diversity. The cytological features of MC are diverse and may lack overt feature of malignancy. Pathologists should be aware of this entity while evaluating cytological smears of salivary gland mass.

Structure, replication efficiency and fragility of yeast ARS elements.

DNA replication in eukaryotes initiates at specific sites known as origins of replication, or replicators. These replication origins occur throughout the genome, though the propensity of their occurrence depends on the type of organism. In eukaryotes, zones of initiation of replication spanning from about 100 to 50,000 base pairs have been reported. The characteristics of eukaryotic replication origins are best understood in the budding yeast Saccharomyces cerevisiae, where some autonomously replicating sequences, or ARS elements, confer origin activity. ARS elements are short DNA sequences of a few hundred base pairs, identified by their efficiency at initiating a replication event when cloned in a plasmid. ARS elements, although structurally diverse, maintain a basic structure composed of three domains, A, B and C. Domain A is comprised of a consensus sequence designated ACS (ARS consensus sequence), while the B domain has the DNA unwinding element and the C domain is important for DNA-protein interactions. Although there are ∼400 ARS elements in the yeast genome, not all of them are active origins of replication. Different groups within the genus Saccharomyces have ARS elements as components of replication origin. The present paper provides a comprehensive review of various aspects of ARSs, starting from their structural conservation to sequence thermodynamics. All significant and conserved functional sequence motifs within different types of ARS elements have been extensively described. Issues like silencing at ARSs, their inherent fragility and factors governing their replication efficiency have also been addressed. Progress in understanding crucial components associated with the replication machinery and timing at these ARS elements is discussed in the section entitled "The replicon revisited".

Dermatofibrosarcoma protuberans in a child: a case report.

Background. Dermatofibrosarcoma protuberans (DFSP) is an intermediate grade soft tissue neoplasm originating from the dermal layer of the skin. It usually occurs in adults; however, it can rarely be seen in infancy and childhood. Diagnosis of DFSP in children is quite difficult-given-rarity of this lesion, its variegated appearance, and its presentation sometimes at unusual sites. Case. We present the case of five-year-old boy who came with painless lesion on a forehead. Fine needle aspiration cytology (FNAC) suggested possibility of mesenchymal neoplasm. Patient was advised excision biopsy. Final diagnosis of DFSP was made based on histopathological findings. The patient was then advised reexcision surgery with wide margins. The patient was lost to followup and later turned up after two months with recurrence of a similar swelling at the same site. Conclusion. DFSP in children is rare and difficult to diagnose. Treatment of childhood DFSP is often delayed leading to incomplete excision. Hence, there is need to recognize and appropriately manage this uncommon childhood neoplasm.