Non small cell Carcinoma- Lung: Distribution and spectrum of mutations among patients in Eastern India

Background: Lung cancer is one of the most common malignancies in the world. About 80–85% of lung cancers are non-small cell lung cancer (NSCLC). The development of therapeutic agents targeting products of epidermal growth factor receptor (EGFR) gene mutation and anaplastic lymphoma kinase (ALK) rearrangements has significantly improved survival in patients with NSCLC. Thus, the patients eligible for the treatment should be selected through appropriate molecular tests. Objective: The main objective was to study the distribution of NSCLC and its genetic mutations, in the patients of Eastern India. Methodology: A prospective study was carried out among 228 patients, in a tertiary care hospital of Eastern India during a period of 2 years from January 2016 to January 2018. We have included all the patients who were screened and found to have lug carcinoma. The detailed clinical history of the patients was recorded. We have used techniques such as radiology, histopathology, immunohistochemistry (IHC) and molecular study by FISH technique. Results: Out of 138 cases of NSCLC on histopathology 78 cases (56.7%) were reported as squamous cell carcinoma, 46 cases (33.3%) as adenocarcinoma and 14 cases (10.1%) as NSCLC. IHC was used for categorization of NSCLC cases which showed adenocarcinoma in 4 patients and squamous cell carcinoma in 10 patients. EGFR exon 19 deletion mutation was the predominant mutation in adenocarcinoma. Conclusion: Molecular study for genetic analysis has improved the scope for targeted therapy in Nonsmall cell carcinoma patients, thereby reducing mortality and morbidity in cases of lung carcinoma

Endometrial Stromal Tumour: Clinicopathological Series of Seven Cases

Endometrial Stromal Tumour (EST) mimics other neoplasms and is difficult to diagnose due to its wide range of morphologies. This is a clinicopathological study of seven cases of EST, which includes Endometrial Stromal Nodule (ESN), Low-grade Endometrial Stromal Sarcoma (LGESS), and High-grade Endometrial Stromal Sarcoma (HGESS). The age ranges from 34 to 75 years. Five out of seven cases presented with abnormal uterine bleeding, abdominal pain, and were radiologically suspected to be leiomyomas. After histopathological and Immunohistochemical (IHC) examination, one was diagnosed as ESN, three as LGESS, and the remaining three cases as HGESS. One case was initially diagnosed as a cellular leiomyoma and experienced multiple recurrences, eventually being diagnosed as HGESS with a fatal outcome within 36 months of the onset of the first symptoms. ESN and LGESS should be differentiated from leiomyoma and leiomyosarcoma. IHC plays an important role in distinguishing these tumours from the more common smooth muscle counterparts

Invasion of ovarian cancer cells is induced by PITX2-mediated activation of TGF-β and Activin-A

Background:Most ovarian cancers are highly invasive in nature and the high burden of metastatic disease make them a leading cause of mortality among all gynaecological malignancies. The homeodomain transcription factor, PITX2 is associated with cancer in different tissues. Our previous studies demonstrated increased PITX2 expression in human ovarian tumours. Growing evidence linking activation of TGF-β pathway by homeodomain proteins prompted us to look for the possible involvement of this signalling pathway in PITX2-mediated progression of ovarian cancer. Methods: The status of TGF-β signalling in human ovarian tissues was assessed by immunohistochemistry. The expression level of TGFB/INHBA and other invasion-associated genes was measured by quantitative-PCR (Q-PCR) and Western Blot after transfection/treatments with clones/reagents in normal/cancer cells. The physiological effect of PITX2 on invasion/motility was checked by matrigel invasion and wound healing assay. The PITX2- and activin-induced epithelial-mesenchymal transition (EMT) was evaluated by Q-PCR of respective markers and confocal/phase-contrast imaging of cells. Results: Human ovarian tumours showed enhanced TGF-β signalling. Our study uncovers the PITX2-induced expression of TGFB1/2/3 as well as INHBA genes (p < 0.01) followed by SMAD2/3-dependent TGF-β signalling pathway. PITX2-induced TGF-β pathway regulated the expression of invasion-associated genes, SNAI1, CDH1 and MMP9 (p < 0.01) that accounted for enhanced motility/invasion of ovarian cancers. Snail and MMP9 acted as important mediators of PITX2-induced invasiveness of ovarian cancer cells. PITX2 over-expression resulted in loss of epithelial markers (p < 0.01) and gain of mesenchymal markers (p < 0.01) that contributed significantly to ovarian oncogenesis. PITX2-induced INHBA expression (p < 0.01) contributed to EMT in both normal and ovarian cancer cells. Conclusions: Overall, our findings suggest a significant contributory role of PITX2 in promoting invasive behaviour of ovarian cancer cells through up-regulation of TGFB/INHBA. We have also identified the previously unknown involvement of activin-A in promoting EMT. Our work provides novel mechanistic insights into the invasive behavior of ovarian cancer cells. The extension of this study have the potential for therapeutic applications in future

Redox homeostasis and age-related deficits in neuromuscular integrity and function

Skeletal muscle is a major site of metabolic activity and is the most abundant tissue in the human body. Age-related muscleatrophy (sarcopenia) and weakness, characterized by progressive loss of lean muscle mass and function, is a major contributorto morbidity and has a profound effect on the quality of life of older people. With a continuously growing older population(estimated 2 billion of people aged >60 by 2050), demand for medical and social care due to functional deficits, associatedwith neuromuscular ageing, will inevitably increase. Desp ite the importance of this ‘epidemic’ problem, the primarybiochemical and molecular mechanisms underlying age-related deficits in neuromuscular integrity and function have not beenfully determined. Skeleta l muscle generates reactive oxygen and nitrogen species (RONS) from a variety of subcellular sources,and age-associated oxidative damage has been suggested to be a major fac tor contributing to the initiation and progression ofmuscle atrophy inherent with ageing. RONS can modulate a variety of intracellular signal transduction processes, anddisruption of these events over time due to altered redox control has been proposed as an underlying mechanis m of ageing.The role of oxidants in ageing has been extensively examined in different model organisms that have undergone geneticmanipulations with inconsistent findings. Transgenic and knockout rodent studies have provided insight into the function ofRONS regulatory systems in neuromuscular ageing. This review summarizes almost 30 years of research in the field of redoxhomeostasis and muscle ageing, providing a detailed discussion of the experimental approaches that have been undertaken inmurine models to examine the role of redox regulation in age-related muscle atrophy and weakness

Intramedullary tumors in children

Intramedullary tumors of the spinal cord account for 35-40% of intraspinal tumors in children. The biological behavior of these tumors is of slow progression, and hence aggressive surgery has been advocated. Surgical adjuncts include use of intraoperative neurophysiological monitoring, preoperative ultrasound, microsurgical techniques and ultrasonic suction devices. Osteoplastic laminoplasty approaches avoid post-laminectomy deformities in younger children. Postoperative radiotherapy and more recently chemotherapy regimes have been proposed for incompletely resected tumors

Primary aspergillosis of vocal cord: Long-term inhalational steroid use can be the miscreant

Primary laryngeal aspergillosis is extremely rare, especially in an immunocompetent host. It is commonly found as a part of systemic infection in immunocompromised patients. A case of vocal cord aspergillosis with no systemic extension in an immunocompetent patient on long-term steroid metered dose inhaler (MDI) is presented here, because of its rarity. The present case is a 28-year-old asthmatic female who was on inhalational steroid for 8 years, presented with sudden onset of severe dysphonia for 5 days. Fiberoptic laryngoscopy demonstrated whitish plaque involving right vocal cord, clinically suggestive of fungal laryngitis. Microlaryngeal laser surgery was performed with stripping of the plaque. Histopathology demonstrated ulcerated hyperplastic squamous epithelium with masses of fungal hyphae, which was confirmed to be Aspergillus species on fungal culture. This rare but serious adverse effect of long-term steroid MDI use must be kept in mind while treating an asthmatic patient. We also present a brief review of literature of laryngeal aspergillosis

En plaque meningioma with angioinvasion

En plaque meningioma is a rare type of meningioma characterized by infiltrative nature, sheet-like growth and at times invading the bone. We report here a case of en plaque meningioma with typical grade I histomorphology along with unusual feature of angioinvasion. The patient was a 55-year-old man presenting with headache and painful proptosis of right eye. Imaging modalities revealed an en -plaque meningioma extending into the right sylvian fissure, with thickening of right temporal calvarium, greater wing of sphenoid and extension into the orbit. Magnetic resonance angiography showed medial displacement of right middle cerebral artery. The tumor was removed from the sylvian fissure and right temporal convexity. However, only subtotal removal of the intraorbital part was possible. Histology showed a meningothelial meningioma with low tumor cell proliferation, but infiltration into the bone, skeletal muscle and angioinvasion. Recognition of meningiomas en plaque is useful, as these tumors are difficult to resect completely, and are more prone to undergo recurrence or malignant change. In addition, angioinvasion seen in this tumor may have additional prognostic significance

Leydig cell tumor : A report of two cases with unusual presentation

Leydig cell tumors (LCTs) are rare testicular tumors. They constitute 1-3&#x0025; of all testicular tumors. We report two cases of LCT, one benign and the other one malignant, representing both ends of the spectrum. The case of benign LCT presented with infertility and was found to have azoospermia, and subsequently underwent orchidectomy. Histopathologic examination revealed the presence of a benign LCT. Postoperative recovery was uneventful. The sperm count improved subsequently, and a year later, he fathered a child. The case of malignant LCT was seen in another 47 year old male who presented with cough. On examination, a testicular swelling was found, and after orchidectomy, he was diagnosed to have malignant LCT on histopathologic examination

Xanthogranulomatous pyelonephritis and renal tubulopapillary adenomas: A rare coexistence

Xanthogranulomatous pyelonephritis is an uncommon inflammatory condition accounting for 1% of chronic pyelonephritis cases. Clinically and radiologically it mimics other renal space occupying lesions. Hence, correct preoperative diagnosis is not possible in all cases and nephrectomy is done in most patients. Renal tubulopapillary adenomas are benign epithelial lesions of kidney found to be associated with papillary renal cell carcinoma, acquired renal cystic disease, long term hemodialysis, arteriosclerotic renal vascular disease, etc. Here, we report two cases of Xanthogranulomatous pyelonephritis associated with the rare finding of renal tubulopapillary adenomas