An Unusual Mixed Thyroid Carcinoma: A Surgical and Pathological Rarity.

The incidence of mixed thyroid carcinoma of poorly differentiated thyroid carcinoma (PDTC) and papillary carcinoma thyroid is very unusual. PDTC exhibits a high degree of dedifferentiation and histopathological confirmation is done based on Turin's criteria. This type of carcinoma has a poor prognosis and the survival rates at five and ten years post-diagnosis are significantly lower compared to well-differentiated thyroid carcinomas. Surgery is the best mode of treatment at present. This is a case of a 71-year-old female who underwent total thyroidectomy with modified radical neck dissection which yielded a histopathological variant comprising PDTC and papillary thyroid carcinoma. The patient was followed up with a serial thyroglobulin antibody test and ultrasound of the neck at six months and one year, and both were found to be normal.

Hypertrophic Lichen Planus: A Precursor Lesion for Squamous Cell Carcinoma.

Squamous cell carcinoma (SCC) is the second most common malignant tumor of the skin. This case report aims to report a case of cutaneous squamous cell carcinoma in an elderly male presenting with a non-healing ulceroproliferative growth on the shin of the right lower limb and a hypopigmented patch on the shin of the left lower limb. The significant feature of this case is that in the shin of the left lower limb, SCC appears in the background of chronic hypertrophic lichen planus (HLP) but in the right lower limb, there is no evidence of a background hypertrophic lichen planus. There are only a few similar cases reported so far in the literature showing long-standing hypertrophic lichen planus as a risk factor for the development of cutaneous squamous cell carcinoma. This case illustrates that chronic hypertrophic lichen planus should be considered as a potential precursor lesion for SCC. Regular screening is essential for early detection, enabling timely intervention for improving patient outcomes.

Expression of Vascular Endothelial Growth Factor (VEGF) in Colorectal Adenoma and Carcinoma in a Tertiary Care Center.

INTRODUCTION:  Colorectal cancer is one of the malignancies in which angiogenesis has been implicated and its importance at different stages of malignant disease. Neovascularization begins when the angiogenic switch is turned on and when angiogenesis activators outweigh angiogenic inhibitors. The process of blood vessel formation is regulated through several growth factor systems. The vascular endothelial growth factor (VEGF) system is one of the important ones and may consequently be a key system in relation to different aspects of colorectal carcinoma treatment. Because of the well-defined steps in its progression (adenoma - Tis - T1 invasive cancer- T2 advanced cancer with metastases), colorectal cancer (CRC) represents a model for investigating the effects of angiogenesis throughout tumor development.  The aim of this study is to determine the role of VEGF expression by immunohistochemistry (IHC) in normal epithelium, dysplasia, carcinoma of colorectal specimens and to correlate the same with tumor grade, stage, nodal status, and metastasis. METHODS: This is a retrospective study on paraffin blocks of 50 colon cancer specimens, 40 adenoma specimens, and 10 normal colonic mucosa specimens. Immunohistochemical stain for VEGF was done on the sections along with controls. Monoclonal antibody detected against VEGF antigen was observed in the cytoplasm of the tumor cells and the intensity of VEGF expression in individual tumor cells was scored on a scale of 0 (no staining) to 3 (strong intensity), and the percentage of cells with VEGF staining at each intensity was estimated from 0 to 100. Pearson's Chi-squared test and Mann-Whitney test were used to determine significant clinicopathological differences between VEGF expression in positive and negative tumors. RESULTS:  In normal epithelium, VEGF immunoreactivity was seen in all 10 cases with high intensity. Among adenomas, VEGF expression was seen in 26 (65%) of the 40 cases. Out of which in tubular adenomas VEGF expression was seen in 13 cases (60%) and negative in eight cases (40%). In tubulo villous adenoma, VEGF expression was seen in nine cases (60%) and negative in six cases (40%). Villous adenomas showed VEGF expression in all four cases (100%). In adenocarcinoma, VEGF expression was seen to be expressed in 42 cases (84%) and negative in eight cases (16%) and expression was higher in low-grade carcinomas (70%) compared to high-grade carcinomas. A significant difference in the expression of VEGF among adenomas and carcinomas was observed with higher intensity present in adenoma when compared to carcinoma. CONCLUSION:  Expression of VEGF could be considered as an early carcinogenic factor in colorectal carcinomas as it is expressed in higher intensity in the precancerous lesion and low-grade and stage 1 adenocarcinoma. Hence, we infer that early colorectal carcinomas are an important model for targeted therapy with antiangiogenic factors for VEGF.

A Case of Multiple Plexiform Schwannomas.

Schwannoma is a slow-growing nerve sheath tumour comprising differentiated neoplastic Schwann cells. The plexiform variant of schwannoma grows in a plexiform or multinodular pattern and may be conventional or of cellular type. Clinically, they manifest as single, skin-coloured tumours along the distribution of peripheral or cranial nerves. This tumour usually ranges between 2 and 4 cm in size, common sites of localization being the head or the flexor aspect of the extremities. The tumour may be associated with neurofibromatosis Type 2 (but not with neurofibromatosis Type 1). The majority are biphasic tumours containing compact areas (Antoni A tissue) showing occasional nuclear palisading (Verocay bodies), alternating with loosely arranged foci (Antoni B tissue). Here, we report a case of a 37-year-old female patient, with complaints of swellings over the right forearm, right wrist and right hand. Biopsy specimens were sent from each of the swellings for histopathological evaluation. The final impression of plexiform schwannoma was made based on the microscopical examination of hematoxylin-and-eosin-stained sections.

A microRNA binding site polymorphism in the 3' UTR region of VEGF-A gene modifies colorectal cancer risk based on ethnicity: a meta-analysis.

BACKGROUND: Vascular endothelial growth factor A (VEGF-A) plays an integral role in angiogenesis by contributing to growth, development, and metastasis of solid tumors. Recently, a single-nucleotide polymorphism +936C/T located in the VEGF-A 3' untranslated region (UTR) facilitated the susceptibility of colorectal cancer. The association between VEGF-A gene polymorphism +936C/T and colorectal cancer risk has been widely studied in the last decade, but presently, the results furnished remain enigmatic. Hence, the study aimed to investigate the association between VEGF-A +936C/T miRNA binding site polymorphism and the risk of developing colorectal cancer. METHODS: This meta-analysis included 13 published case-control studies covering 3465 cases (colorectal cancer) and 3476 healthy controls. Publication bias was examined by means of Begg's funnel plots and Egger's regression tests. The quality of the studies included was evaluated using Newcastle-Ottawa scale. Subgroup analyses were performed in accordance to the various ethnicities of the study subjects and the study quality. RESULTS: From the data obtained, it is implied that VEGF-A +936C/T polymorphism did not correlate with elevated colorectal cancer risk in all genetic models. But the results acquired from the subgroup analysis in over dominant model (CT vs. CC + TT: OR = 1.5047, 95% CI = 1.19-1.90) suggest that VEGF-A +936C/T polymorphism leads to the raise in the risk of developing CRC among the East Asian population. No association was observed in Caucasian and South Asian population. CONCLUSIONS: Our results indicate that VEGF-A +936C/T polymorphism is not a risk factor for developing CRC in Caucasian and South Asian population. However, the East Asian population was related to an increased risk of developing colorectal cancer due to the presence of the minor allele.

Solitary Dermal Cylindroma in an Uncommon Site: A Rare Case Report.

Cylindroma, a benign skin appendage tumor, mostly occurs in the head and neck region. They present as pink to purple, smooth-surfaced, solitary or multiple nodular lesions, mostly affecting middle-aged and elderly women. A clinical diagnosis of cylindroma is unusual but must be considered clinically. We report an unusual case of solitary benign dermal cylindroma that occurred in an uncommon site in a 54-year-old female. She came with complaints of painful swelling on the left side of her chest wall for six months. Histopathological examination of the mass revealed a well-defined tumor composed of nests and islands of a dual population of tumor cells surrounded by pink basement membrane-like material. These nests of cells are arranged in a "jigsaw" puzzle fashion, which is typical of cutaneous cylindroma. The thick pink material surrounding the epithelial cell islands is periodic acid Schiff stain (PAS) positive.

Role of Nrf2 dysfunction in the pathogenesis of diabetic nephropathy: Therapeutic prospect of epigallocatechin-3-gallate.

Diabetic nephropathy (DN), a progressive kidney disease afflicts more than 20 and up to 40% of the diabetic population and it is characterized by persistent microalbuminuria declined glomerular filtration rate. The interesting feature associated with DN is that, even though the progression of the disease correlates with oxidative stress, Nrf2, the master regulator of antioxidant defense system involved in counteracting oxidative stress is also upregulated in the diabetic kidneys of both human as well as experimental animals in early stages of DN. Despite the increased expression, the ability of this protein to get translocated into the nucleus is diminished signifying the functional impairment of Nrf2, implying redox imbalance. Hence, it is understood that agents that boost the translocation of Nrf2 might be beneficial rather than those that quantitatively overexpress Nrf2 in treating DN. The deleterious effects of synthetic Nrf2 activators have instigated the researchers to search for phytochemicals that have ambient Nrf2 boosting ability with no side effects, one such phytochemical is Epigallocatechin-3-gallate (EGCG) and it has shown beneficial effects by preventing the progression of DN via influencing Nrf2/ARE pathway, however, the modus operandi is unclear, despite speculations. This study was designed to find out whether supplementation of Nrf2 booster like EGCG at the crucial time of Nrf2 dysfunction can mitigate the progression of DN. Based on the findings of the present study, it might be concluded that the beneficial effect of EGCG in mitigating DN is mediated mainly through its ability to activate the Nrf2/ARE signaling pathway at multiple stages i.e., by downregulating Keap1 and boosting the nuclear Nrf2 level by disrupting Nrf2-Keap1 interaction. These results emphasize that supplementation of EGCG might be more beneficial at an early stage of DN, where dysfunctional Nrf2 accumulation occurs, which should be further validated.

Bladder neoplasms and NF-κB: an unfathomed association.

Introduction: Bladder cancer is the second most common genitourinary tract cancer and is often recurrent and/or chemoresistant after tumor resection. Cigarette smoking, exposure to aromatic amines, and chronic infection/inflammation are bladder cancer risk factors. NF-κB is a transcription factor that plays a critical role in normal physiology and bladder cancer. Bladder cancer patients have constitutively active NF-κB triggered by pro-inflammatory cytokines, chemokines, and hypoxia, augmenting carcinogenesis and progression.Areas covered: NF-κB orchestrates protein interactions (PTEN, survivin, VEGF), regulation (CYLD, USP13) and gene expression (Trp 53) resulting in bladder cancer progression, recurrence and resistance to therapy. This review focuses on NF-κB in bladder inflammation, cancer and resistance to therapy.Expert opinion: NF-κB and bladder cancer necessitate further research to develop better diagnostic and treatment regimens that address progression, recurrence and resistance to therapy. NF-κB is a master regulator that can act with or on minimally one cancer hallmark gene or protein, leading to bladder cancer progression (Tp53, PTEN, VEGF, HMGB1, CYLD, USP13), recurrence (PCNA, BcL-2, JUN) and resistance to therapy (P-gp, twist, SETD6). Thus, an understanding of bladder cancer in relation to NF-κB will offer improved strategies and efficacious targeted therapies resulting in minimal progression, recurrence and resistance to therapy.

Investigating the role of microRNA-27a gene polymorphisms and its interactive effect with risk factors in gastrointestinal cancers.

Gastrointestinal (GI) cancers are known to have a high incidence worldwide and require an early diagnosis to successfully treat them, providing higher survival rates and better quality of life for the patients. MicroRNA-27a is a well-known oncogene that plays a significant role in various GI cancers. It is known to upregulate the expression of numerous oncogenes leading to cancer progression. The miR-27a harbors two polymorphisms rs895819 and rs11671784 which alter the disease susceptibility by interfering with the maturation and expression of miR-27a. In the current study, we aimed to investigate the role played by these polymorphisms in cancers of the GI tract. We conducted a case-control study with 210 GI cancer cases and 210 cancer-free controls to analyze the effect of these polymorphisms. The rs895819 polymorphism was genotyped using PCR-RFLP, and rs11671784 was genotyped on a MassARRAY platform. The association analysis failed to bring out any significant association of the polymorphisms with GI cancer risk. However, genotype-phenotype interaction analysis revealed that the rs895819 was found to increase the risk GI cancers along with the presence of risk factors such as socioeconomic status, diabetes mellitus, hypertension, alcohol consumption, and tobacco chewing.

Novel clinical phenotype of generalised lymphatic dysplasia in a neonate: a missed diagnosis.

We report a preterm neonate who had a large cervical cystic hygroma and right chylothorax. She was operated on day-21 and a near-complete resection of cystic hygroma was done. She developed refractory hypoxemia and shock post surgery and died after 24 hours. During autopsy, the chest cavity was found to be filled with chyle. Histopathological examination showed dilated lymphatics in the pleura, hepatic capsule, serosa of stomach and intestines, peri-pancreatic regions, peri-renal capsule and peri-adrenal tissues suggestive of generalised lymphatic dysplasia. Clinical exome sequencing did not reveal any pathogenic mutation in the genes involved in primary lymphatic dysplasia, noonan syndrome or rasopathies.

Sixty-four-year-old man with non-productive cough and lung mass.

A 64-year-old manpresented with non-productive cough and dyspnoea and was evaluated and diagnosed to have a left lung mass on CT of the chest. A transthoracic needle biopsy under CT guidance revealed necrotic tissue on histopathology and was inconclusive. Positron emission tomography scan revealed a fluoro-deoxyglucose-avid left lung mass with a left upper lobe luminal cut-off. A flexible video bronchoscopy was performed and revealed left upper lobe complete obstruction with an endoluminal plug which was removed in piecemeal fashion, and deeper biopsies were taken from the lingula. Histopathology revealed underlying adenocarcinoma colonised by aspergillosis. This case serves to remind us of the possibility of missing underlying malignancy when taking superficial biopsies of clearly visualised endobronchial necrotic tissue and the need for debulking it to a reasonable extent and to take deeper biopsies in order to not miss a possible underlying malignancy.

Differential expression of NF-κB heterodimer RelA/p50 in human urothelial carcinoma.

BACKGROUND: Urothelial carcinoma (UC) is the fifth most common malignancy that accounts for 5% of all cancers. Diagnostic markers that predict UC progressions are inadequate. NF-κB contributes towards disease progression upon constitutive activation in many solid tumors. The nuclear localization of NF-κB indicates increased transcriptional activity while cytoplasmic localization indicates the inactive protein repository that can be utilized readily by a malignant cell. This study delineates the nuclear and cytoplasmic differential expression of NF-κB heterodimers in UC progression. METHODS: The involvement of the NF-κB proteins in UC was analyzed in silico using cytoscape. The expression of NF-κB heterodimers was analyzed by immunohistochemistry. RESULTS: PINA4MS app in cytoscape revealed over expression of RelA and suppression of NF-κB1 (p50 precursor) in UC whereas the expression of NF-κB target proteins remained unhindered. Immunohistochemical localization showed nuclear RelA/p50 in low grade UC whereas in high grade only RelA expression was observed. Conversely, cytoplasmic expression of RelA/p50 remained extensive across high and low grade UC tissues (p < 0.005). RelA nuclear and cytoplasmic expression (p < 0.005) was directly proportional to the disease progression. In our study, some of the high-grade UC tissues with squamous differentiation and muscle invasion had extensive nuclear p50 localization. The phenomenon of RelA/p50 expression seen increased in low-grade UC than high grade UC might be due to their interaction with other members of NF-κB family of proteins. Thus, NF-κB RelA/p50 differential expression may play a unique role in UC pathogenesis and can serve as a biomarker for diagnosis.

Paediatric Peripheral Primitive Neuroectodermal Tumour - A Clinico-Pathological Study from Southern India.

INTRODUCTION: Primitive Neuroectodermal Tumour (PNET)/Ewing Sarcomas (ES) are aggressive childhood malignancies with neuroectodermal differentiation. AIM: To study the clinical presentation, morphology, Immun-ohistochemistry (IHC), management and outcome of all the cases of paediatric pPNET/ES reported in our tertiary care centre over a period of six years. MATERIALS AND METHODS: This was a retrospective study conducted at Sri Ramachandra Medical College and Research Institute, Chennai, India. All biopsy proven cases of peripheral PNET/ES, in patients less than 18 years of age for a period of six years were included in this study. The corresponding clinical details regarding initial presentation, treatment and follow up were retrieved from the case files and analysed. Survival rate was calculated and Kaplan-Meier survival curve was plotted. RESULTS: We describe eleven cases of paediatric peripheral PNET/ES. The mean age at presentation was 94.08 (±58.27) months with a male/female ratio of 1.2:1. About 27.3% cases, all male with a mean age of 140 months at presentation, had distant metastasis during initial diagnosis. Biopsy showed small round blue cell morphology on light microscopy. IHC revealed strong membranous staining for CD99 in all cases. All children were treated with neo-adjuvant chemotherapy and then surgery, followed by radiotherapy if indicated. The cases were followed up for a mean duration of 20.82 months (ranging from one to 66 months). Nine children are doing well on follow up (81.8% survival rate). Two cases with metastasis at initial presentation died. Patients with metastatic disease exhibited a mean duration of survival of 9.66 (±7.24) months and those with localized disease exhibited a mean duration of survival of 25 (±22.88) months. CONCLUSION: Metastasis at diagnosis is the single most important factor affecting prognosis. This was reflected in the present study where cases with metastasis exhibited a short mean duration of survival when compared to localized disease. It is likely that many cases of PNET/ES were not accurately identified in the past as IHC plays a vital role in the diagnosis of these small round blue cell tumours. IHC in adjunct with molecular studies has improved diagnostic accuracy. Multidisciplinary management and good supportive care when the lesion is localized has lead to improved survival.

Impact of EGCG Supplementation on the Progression of Diabetic Nephropathy in Rats: An Insight into Fibrosis and Apoptosis.

Apoptosis is an active response of cells to altered microenvironments, which is characterized by cell shrinkage, chromatin condensation, and DNA fragmentation, in a variety of cell types such as renal epithelial cells, endothelial cells, mesangial cells, and podocytes. Hyperglycemia is among the microenvironmental factors that may facilitate apoptosis, which plays a decisive role in the initiation of diabetic nephropathy. Transforming growth factor-ß emerges as a powerful fibrogenic factor in the development of renal hypertrophy. Although, a number of potential treatment strategies exist for diabetic nephropathy, considering the ease of use and bioavailability, phytochemicals stands distinct as the preeminent option. EGCG, a green tea catechin is one such phytochemical which possesses hypoglycemic and antifibrotic activity. The present study aims to explore the potential of EGCG to prevent apoptosis in a high-fat diet and STZ induced diabetic nephropathy rats by assessing renal function, pro-fibrotic marker, and the expression of apoptotic and antiapoptotic proteins. Our results validate EGCG as a potential antiapoptotic agent evidently by improving renal function via down regulating TGF-ß, consequently ameliorating diabetic nephropathy. In accordance with this, EGCG might be regarded as a prospective therapeutic candidate in modulating diabetic nephropathy, thus being a promising treatment.

Bilateral Synchronous Paratesticular Leiomyoma - A Rare Entity.

Paratesticular region is an obscure anatomical region that includes spermatic cord and its contents, tunica of the testes, epididymis and appendices of epididymis and testis. Paratesticular tumours may closely resemble and be clinically indistinguishable from testicular tumours, resulting in a diagnostic dilemma. Preoperative distinction between the benign and malignant paratesticular tumour is extremely difficult, resulting in difficulty in diagnosis and management. We hereby present a case of a 56-year-old male who reported with a painless bilateral scrotal mass and underwent surgical excision of the same. The final biopsy report was paratesticular leiomyoma. The main purpose of this manuscript is to emphasize on the fact that it is imperative for the treating urologists to be aware of such potentially benign rare entity. A high index of clinical suspicion is mandatory, as lack of knowledge about this condition would result in an unnecessary radical orchidectomy.

Double Pathology: Malignant Epithelial Ovarian Tumor and Germ Cell Tumor (Choriocarcinoma), a Rare Coexistence.

Surface epithelial stromal tumors account for approximately 60% of all ovarian tumors and approximately 90% of all ovarian malignancies. Sex cord stromal tumors account for 7% of all malignant ovarian tumors. Germ cell tumors make up only 3-7% of malignant ovarian tumors. A combination of serous carcinoma of the ovary and choriocarcinoma is rare. Until today such combination has been documented only in six cases in the English literature. Here, we describe a case of ovarian serous carcinoma, where histopathology revealed a combination of serous carcinoma with adjacent choriocarcinoma component in the extraovarian peritoneal deposits. A 64-year-old post-menopausal female was diagnosed to have stage IV ovarian cancer. She received six cycles chemotherapy. Subsequently she underwent optimal cytoreductive surgery. Microscopically, monomorphic histology (serous carcinoma) was noted in both the ovaries and dimorphic histologies (serous carcinoma and choriocarcinoma) in the sigmoid mesocolon nodule, omentum and left subdiaphragmatic nodules. Metronomic chemotherapy continued and patient is on regular follow-up for the past 1 year with stable disease. Recognition of choriocarcinomatous components in ovarian carcinomas is important because of its association with aggressive behavior. In spite of the aggressive histology, the patient is surviving for the past 1 year. Different chemotherapeutic regimens have been used in cases of mixed choriocarcinoma and carcinoma, but established chemotherapeutic regimens have not been described. Chemotherapeutic regimens that target both components have been advocated and used. The absence of choriocarcinoma in ovarian primary and its presence in the extraovarian peritoneal deposits have not been described in the English literature so far. This case is being presented for its rarity.

Magnetic resonance signal intensity measurements in the diagnosis of fetal central nervous system anomalies.

OBJECTIVES: To evaluate the possible role of Magnetic Resonance (MR) signal intensity measurements in diagnosing Central Nervous System (CNS) anomalies antenatally. METHODS: MR images of 110 fetal brains between 18 and 38 weeks were studied. Nine were excluded due to destroyed brain. 50 had CNS anomalies. 51 had normal CNS and were used as controls. Regions of interest (ROI) cursors were placed in Vitreous, cerebellar vermis, thalamus, frontal white matter, corona radiata, periventricular region and grey matter. The lateral ventricle diameters were also obtained. Signal intensity ratio (SIR) was calculated by the signal intensity of each of the above regions to that of the vitreous. SIR in controls were compared with fetuses having: (1) Hydrocephalus. (2) Arnold Chiari type-2 Malformation (ACM-2) (3) Non-progressive ventriculomegaly (4) Miscellaneous CNS anomalies. The correlation of the normalcy or abnormalcy of the brain was based on Clinical/Physical examination in 51, Ultrasound in 20, MRI in 2 and autopsy in 28. RESULTS: In hydrocephalus and ACM-2, the SIR of vermis and periventricular region were higher than controls whereas in non-progressive ventriculomegaly and miscellaneous CNS anomalies there was no significant difference. CONCLUSION: Signal intensity measurements are useful to differentiate physiological and non-progressive ventriculomegaly from hydrocephalus and ACM-2.

Study of endometrial pathology in abnormal uterine bleeding.

INTRODUCTION: Abnormal uterine bleeding (AUB) is the commonest presenting symptom in gynaecology out-patient department. Endometrial sampling could be effectively used as the first diagnostic step in AUB, although at times, its interpretation could be quite challenging to the practicing pathologists. This study was done to evaluate histopathology of endometrium for identifying the endometrial causes of AUB. We also tried to observe the incidence of various pathology in different age groups presenting with abnormal uterine bleeding. MATERIAL AND METHODS: This was a study done at Sri Ramachandra Medical College and Research Institute, Chennai, India on 620 patients who presented with AUB from June 2005-June 2006. Out of which 409 cases of isolated endometrial lesions diagnosed on histopathology were selected for the final analyses. A statistical analysis between age of presentation and specific endometrial causes was done using χ(2) test. RESULTS: The most common age group presenting with AUB was 41-50 years (33.5%). The commonest pattern in these patients was normal cycling endometrium (28.4%). The commonest pathology irrespective of the age group was disordered proliferative pattern (20.5%). Other causes identified were complications of pregnancy (22.7%), benign endometrial polyp (11.2%), endometrial hyperplasias (6.1%), carcinomas (4.4%) and chronic endometritis (4.2%). Endometrial causes of AUB and age pattern was statistically significant with P value <0.05. CONCLUSION: There is an age specific association of endometrial lesions. In perimenopausal women AUB is most commonly dysfunctional in origin and in reproductive age group, one should first rule out complications of pregnancy. The incidence of disordered proliferative pattern was significantly high in this study, suggesting an early presentation of these patients.