Papillary tumor of pineal region: report of three cases and review of literature.

Papillary tumors of the pineal region (PTPRs) are rare and are recognized as a distinct entity in the recent 2007 World Health Organization (WHO) classification of tumors of nervous system. Till date, only 55 cases have been reported. We report another three patients of PTPRs with characteristic radiological features. Histologically, all the three patients exhibited remarkable uniform histology of epithelioid morphology with variable presence of single to multilayered papillary architecture. Consistent absence of fibrillary matrix was noted in all the three cases. None of the cases showed aggressive histology. A large multicenter study is essential for upfront characterizing the biological behavior, as frequency of these tumors is very low.

Intracranial growing teratoma syndrome following radiotherapy--an unusually fulminant course.

INTRODUCTION: Residual radiologically progressive masses following multimodality treatment of malignant mixed intracranial germ cell tumors are described. Often these enlarge, and this is called the growing teratoma syndrome. A similar phenomenon during radiotherapy alone has not been described. SUBJECTS AND METHODS: A 5-year old boy presented with features of raised intracranial pressure. Imaging revealed a posterior third ventricular mass, which was biopsied endoscopically. RESULTS: A review of the scanty tissue was suggestive of a pineal parenchymal tumor, and hence radiation was planned. After just ten fractions, he developed rapid neurological deterioration. Repeat imaging raised a possibility of a teratomatous tumor. He underwent emergency excision. However, he had a stormy postoperative course and succumbed to deep venous infarction. Histology revealed a purely mature teratoma. CONCLUSION: Though a growing teratoma syndrome has been described following chemotherapy, no such report while on radiation exists. Ours could be the first such reported case. We discuss the possible mechanisms with a review of the literature.

An SNP linkage scan identifies significant Crohn's disease loci on chromosomes 13q13.3 and, in Jewish families, on 1p35.2 and 3q29.

Inflammatory bowel disease (IBD) is a complex genetic disorder of two major phenotypes, Crohn's disease (CD) and ulcerative colitis (UC), with increased risk in Ashkenazi Jews. Twelve genome-wide linkage screens have identified multiple loci, but these screens have been of modest size and have used low-density microsatellite markers. We, therefore, performed a high-density single-nucleotide polymorphism (SNP) genome-wide linkage study of 993 IBD multiply affected pedigrees (25% Jewish ancestry) that contained 1709 IBD-affected relative pairs, including 919 CD-CD pairs and 312 UC-UC pairs. We identified a significant novel CD locus on chromosome 13p13.3 (peak logarithm of the odds (LOD) score=3.98) in all pedigrees, significant linkage evidence on chromosomes 1p35.1 (peak LOD score=3.5) and 3q29 (peak LOD score=3.19) in Jewish CD pedigrees, and suggestive loci for Jewish IBD on chromosome 10q22 (peak LOD score=2.57) and Jewish UC on chromosome 2q24 (peak LOD score=2.69). Nominal or greater linkage evidence was present for most previously designated IBD loci (IBD1-9), notably, IBD1 for CD families at chromosome 16q12.1 (peak LOD score=4.86) and IBD6 in non-Jewish UC families at chromosome 19p12 (peak LOD score=2.67). This study demonstrates the ability of high information content adequately powered SNP genome-wide linkage studies to identify loci not observed in multiple microsatellite-based studies in smaller cohorts.

Orbital medulloepitheliomas -- with extensive local invasion and metastasis: a series of three cases with review of literature.

Intraocular medulloepithelioma is a rare embryonal neoplasm which usually presents in childhood as a ciliary body mass. This tumor is usually confined to the orbit and rarely tends to be locally aggressive and metastatic. We describe three rare cases of metastatic malignant teratoid medulloepithelioma. The patients were males aged 7, 16 and 25 years with right eye involvement in all the cases. All patients had local recurrence (multiple in two) and metastasis to the intraparotid and cervical lymph nodes. Distinction from round cell tumors and primary salivary gland neoplasms occurring in the parotid gland is strongly warranted, especially in biopsy samples, because the biological behaviour and treatment of medulloepithelioma differs greatly from the above lesions.

Morphological spectrum of AIDS-related plasmablastic lymphomas.

We have had a recent spurt in cases of AIDS-related lymphoma (ARL) at our centre. Most of these cases are aggressive mature B cell lymphomas, mainly plasmablastic lymphoma (PBL) and diffuse large B-cell lymphoma (DLBCL). Most of the PBL are extranodal in location and are mucosa-based. We reviewed the morphological features of 34 cases of PBL. Diagnosis was based on morphology, immunohistochemistry, proliferation index, HIV positive status and its preference to extranodal sites (mostly mucosa based). We classified PBL into three morphological subtypes (immunoblastic - 25, Burkitt's - 7, plasmacytic - 2). Tumor cells expressed as leucocyte common antigen (LCA) in 60%, CD138 in 100%, EMA in 45% and light chain restriction in 86% cases. CD20 was negative in all cases. Pathologists need to be aware of PBL and its various morphological subtypes as the identification of this entity from its close differentials carries major therapeutic implications.

Laryngeal chondrometaplasia: a great mimic of chondrosarcoma.

Chondrometaplasia of larynx is a rare entity with an unknown etiopathogenesis. The lesion remains asymptomatic unless it reaches a large size and a history of trauma is usually elicited. It is a known pitfall in diagnostic evaluation and a clinically significant differential considered in evaluation of cartilaginous tumors of the larynx. A 66-year-old man presented with a nodular mass of right side of neck, progressive hoarseness of voice and pain, and a suspicious growth in the right glottic region. A CT followed by an MRI one month later revealed a slow growing ill defined thickening and enhancement of the supraglottic soft tissues, predominantly involving the submucosa, along the greater cornu on the left side of the thyroid cartilage, with extra-chondral enhancement and was suggested to be of infectious etiology. On neck exploration a lesion clinically suspected to be a chondrosarcoma was excised along with the right ala of the thyroid cartilage. The tissue processed entirely, revealed features consistent with chondrometaplasia of larynx. The importance of distinguishing this lesion from cartilaginous tumors is emphasized.

Solitary fibrous tumour: a diagnostic dilemma.

Solitary fibrous tumour (SFT) is a rare spindle cell neoplasm arising at pleural and extrapleural sites. Five cases of SFT diagnosed at our institution over a five year period were reviewed. Haematoxylin and eosin stained histological sections, immuno-histochemical markers including CD34 and electron microscopy were the different methods used to study these tumours. Three histological features were consistently observed in all the tumours: the tumours were composed of short spindle cells separated by dense collagen bands and arranged in alternate hypocellular and hypercellular areas. CD34 positivity was seen in all the cases. SFT's have been reported to behave in an unpredictable fashion and hence prolonged follow up is essential. Histology, CD34 positivity and electron microscopy are useful tools in diagnosing SFT. While the pleural tumours can be diagnosed based on histology, this must be substantiated by ancillary techniques in case of extrapleural tumours.

Systematic review: adherence issues in the treatment of ulcerative colitis.

Ulcerative colitis is a chronic inflammatory and debilitating disease requiring lifelong treatment. First-line therapy for ulcerative colitis is 5-aminosalicylic acid, which suffers from poor patient adherence outside the clinical trial setting. Formulations to deliver 5-aminosalicylic acid to the disease activity site, both orally and topically, are often inconvenient and require multiple daily dosing. Such regimens can interfere with normal life and reduce the overall quality of life, negatively impacting on treatment adherence and leading to poorer long-term outcomes. These include increased morbidity with an elevated risk of symptomatic relapse, possible greater risk of colorectal cancer and higher overall costs of care. Ulcerative colitis patients cite treatment regimen complexity, tablet quantity and dose frequency as key negative influencers of adherence. Solutions to these issues include addressing patient concerns, simplifying daily regimens and utilizing new formulations such as micropellet and multimatrix oral formulations, rectal gel and once-daily suppository formulations. This review examines the prevalence and impact of non-adherence to 5-aminosalicylic acid therapy among patients with ulcerative colitis, as well as drug delivery strategies that may enhance dosing regimens to improve patient acceptability, adherence and long-term clinical outcomes. It is a combination of understanding patient behaviour, recognizing signs of non-adherent behaviour and utilizing management strategies to change behaviour that will improve patient outcomes.

Depth of invasion is the most significant histological predictor of subclinical cervical lymph node metastasis in early squamous carcinomas of the oral cavity.

AIMS: Cervical node metastasis is the single most important prognostic factor in head and neck squamous carcinomas. Taking a homogenous patient population, applying stringent selection criteria, and standard pathological evaluation methods, this retrospective study aims to establish histological predictors of subclinical cervical node metastasis in early (T1-T2/N0) squamous carcinomas of the oral cavity, thereby identifying a subset of patients who are at an increased risk for cervical node metastasis. METHODS: Forty-eight previously untreated patients with clinically T1 or T2, and N0, squamous carcinomas of the oral cavity who were treated with primary excision of the tumour and elective neck node dissection were selected. Various histological factors including T size, gross and microscopic tumour depth and thickness, grade of differentiation, pattern of invasion, inflammatory response, perineural and lymphovascular invasion were studied. The statistical significance of various parameters as predictors of subclinical node metastasis was determined using logistic regression analysis. RESULTS: Of all the parameters studied, microscopic tumour depth and thickness were the only significant factors (P value=0.026 and 0.046, respectively) which correlated with cervical node metastasis, on univariate analysis. Tumour depth emerged as a single most significant predictor on multivariate analysis. Majority of patients with node metastasis had a tumour depth of more than or equal to 5 mm. CONCLUSION: Depth is the most significant predictor of cervical node metastasis in early squamous carcinomas of the oral cavity. Patients with a tumour depth of more than or equal to 5 mm are at an increased risk of harbouring node metastasis, hence should be taken up for elective node dissection.

Evolution of Papillary Thyroid Carcinoma into Tall Cell Variant and TENIS Syndrome.

We herein report an unusual case of a 55-y-old woman with papillary carcinoma of the thyroid, who presented with multiple recurrences, with its subsequent evolution to tall cell variant and thyroglobulin-elevated negative iodine scintigraphy (TENIS) syndrome. During the course of the disease the lesions became non-iodine-concentrating with an increased proportion of tall cells and evidence of local and distant metastasis. Molecular analysis of the tissue specimen demonstrated BRAFV600E and I582 M mutations along with upregulation of tumor markers in metastatic tissue. The presence of BRAFV600E mutation and other markers warrants further investigation in future studies to define their precise implications for determining the aggressiveness and development into tall cell variant and TENIS.

5-ASA and colorectal cancer chemoprevention in inflammatory bowel disease: can we afford to wait for 'best evidence'?

Patients with inflammatory bowel disease have a higher risk of developing colorectal cancer. The main risk factors for colorectal cancer are not suitable targets for therapeutic intervention, and primary chemoprevention is an intriguing therapeutic option. The analogies between acetyl-salicylic acid and 5-amino-salicylic acid, and the results obtained by using acetyl-salicylic acid as a chemopreventive agent in patients with sporadic colorectal cancer have prompted the study of potential chemopreventive effects of 5-amino-salicylic acid in inflammatory bowel disease. The results of both epidemiological and experimental studies have shown that long-term 5-amino-salicylic acid treatments appear to have a chemopreventive effect. The evidence for this effect is provided by retrospective and case-control studies whose results, however, do not reach the highest grades for evidence-based recommendations. Nevertheless, these results are supported by a series of experimental studies demonstrating the multiplicity of actions of 5-amino-salicylic acid. Although data regarding the chemopreventive effect of 5-amino-salicylic acid may not be rigorous enough to meet the criteria for the highest evidence-based medicine recommendations, we feel that the argument to wait until we have Grade A evidence is not necessarily rational in this case, because discontinuation of 5-amino-salicylic acid treatment to perform a randomised controlled trial would be unethical secondary to their proven efficacy for maintenance treatment.

Follicular dendritic cell tumour of tonsil - is it an under-diagnosed entity?

Neoplasms of follicular dendritic cells are uncommon and while majority of them occur in lymph nodes, they are increasingly recognized at varied sites such as abdominal viscera. Tonsil is the most common extra nodal site for occurrence of FDCT in the head and neck region. We describe three cases of follicular dendritic cell tumour occurring in the tonsil.

Efficacy and safety of certolizumab pegol for Crohn's disease in clinical practice.

BACKGROUND: Certolizumab pegol (CZP) is Food and Drug Administration (FDA)-approved to treat Crohn's disease (CD). However, the efficacy and safety of CZP outside clinical trials are not well established. AIM: To report the efficacy, safety and predictors of response to CZP in CD patients treated during a 6-year period since FDA-approval at a tertiary care centre. METHODS: All CD patients who received CZP at our institution between 2008 and 2013 were evaluated through retrospective medical record-based review of steroid-free complete response (SCR), loss of response and safety. RESULTS: A total of 358 patients were included. One hundred twelve patients (31.3%) and 189 (52.8%) received CZP as their second and third biological agent, respectively. The probability of SCR at 26 week was 19.9% (95% CI, 15.9-24.5). The probability of survival free of loss of response at 2 year was 45.7% (95% CI, 32.5-59.5). A predictor of SCR was age at CD diagnosis of >40 years old (hazard ratio, HR relative to those <17, 4.69; 95% CI, 1.75-12.61). Negative predictors included present perianal fistula (HR, 0.39; 95% CI, 0.16-0.98) and prior primary nonresponse to adalimumab (ADA; HR relative to secondary loss of response, 0.18; 95% CI, 0.04-0.76). Twenty-three patients (6.4%) experienced serious adverse events and 19 patients (5.3%) discontinued CZP due to adverse events. CONCLUSIONS: Certolizumab pegol was both effective and well tolerated for the treatment of Crohn's disease in this large tertiary care centre enriched with biologics-exposed patients. It may be more effective in patients without early-aged Crohn's disease diagnosis, prior primary nonresponse to adalimumab and present perianal fistula.

Novel therapies in the treatment of ulcerative colitis.

Ulcerative colitis is a chronic inflammatory disease of unknown cause. Its course is one of relapse and remission and requires therapy for both the induction and maintenance of remission. The progress in the fields of genetics and immunology has afforded important advances in our understanding of the inflammatory process. Traditional therapy with non-specific anti-inflammatories for ulcerative colitis remains our gold standard as newer targeted therapies have failed to provide any improved efficacy. This review examines the most recent compounds in development for the treatment of ulcerative colitis, including data from early clinical trials and the potential clinical impact of future entities.

Systematic review: short-term adverse effects of 5-aminosalicylic acid agents in the treatment of ulcerative colitis.

AIM: To determine whether there is a difference in short-term adverse events in patients with ulcerative colitis treated with mesalazine, olsalazine or balsalazide. METHODS: MEDLINE was searched for articles published until 2002. Randomized trials of oral mesalazine, olsalazine or balsalazide for the treatment of active disease or the maintenance of remission were included. Outcomes of interest were the frequencies of patients experiencing adverse events and those withdrawn due to adverse events. RESULTS: Forty-six trials were included. One study of mesalazine vs. sulfasalazine for active colitis showed significantly fewer patients with adverse events with mesalazine. Both balsalazide vs. sulfasalazine studies for active disease showed significantly fewer withdrawals with balsalazide. One trial of balsalazide vs. sulfasalazine for maintenance showed significantly fewer patients with adverse events with balsalazide. Otherwise, no significant differences in safety outcomes were noted. CONCLUSION: All three 5-aminosalicylic acid agents are safe in the short term. In mesalazine-treated patients, the frequencies of adverse events or withdrawals due to adverse events were comparable with those in placebo-treated patients and lower than those in sulfasalazine-treated patients. Overall, adverse events or withdrawals were not significantly more frequent with olsalazine than with placebo or sulfasalazine. Adverse events and study withdrawals on balsalazide were less frequent than those on sulfasalazine.

The effectiveness of budesonide therapy for Crohn's disease.

AIM: To assess the effectiveness and safety of budesonide in comparison to corticosteroids, 5-aminosalicylic acid (5-ASA), or placebo for inducing remission of active Crohn's disease and for maintaining remission. STUDY SELECTION CRITERIA: Randomized controlled trials comparing budesonide to corticosteroids, 5-ASA products or placebo were included. Trials had to report on the effectiveness of treatment (defined as decreasing or maintaining Crohn's Disease Activity Index, CDAI, scores < or = 150) or adverse events. DATA ANALYSIS: After assessing the validity of study design and independent, duplicate data extraction from selected trials, summary relative risks (RR) were calculated for each outcome. A test of heterogeneity was also calculated for each outcome using a random effects model. RESULTS: Budesonide was more likely to induce remission than placebo (RR=1.82, 95% CI: 1.15-2.88) or 5-ASA (RR=1.73, 95% CI: 1.26-2.39), although only one trial compared budesonide to 5-ASA products. Although budesonide induced remission less frequently than conventional corticosteroids (RR=0.87, 95% CI: 0.76-0.995), there was no significant difference between conventional corticosteroids and budesonide for inducing remission among patients with a low disease activity (initial CDAI=200-300). Budesonide was significantly less likely to cause corticosteroid-associated adverse events than conventional corticosteroids (RR=0.65, 95% CI: 0.53-0.80). No significant difference in total adverse events or corticosteroid-associated adverse events was demonstrated between budesonide and 5-ASA or placebo. CONCLUSION: Budesonide is significantly more effective than placebo or 5-ASA for inducing remission of active Crohn's disease. Although budesonide is 13% less effective for the induction of remission in active Crohn's disease than conventional corticosteroids, it is less likely to cause corticosteroid-related adverse effects. Budesonide is ineffective in maintaining remission.

Filtration and agar embedding applied to fine needle aspirates for tumor diagnosis by electron microscopy. A combined technique.

OBJECTIVE: To develop a novel method for processing of fine needle aspirates subjected to electron microscopic (EM) study. STUDY DESIGN: Included 70 cases of poorly differentiated malignant tumors in which a definitive diagnosis was not possible on light microscopic (LM) examination and that thus required application of an ancillary technique such as FNA/EM, for diagnosis. We have established a novel method of processing, a technique of filtration through nylon mesh filters to eliminate red blood cells (RBCs) and necrotic debris, followed by agar well embedding to avoid loss of diagnostic material during processing without centrifugation at later steps after agar embedding, thus minimizing the time required for processing. It was successfully carried out in 70 cases. RESULTS: The combined technique was extremely effective in eliminating RBCs and necrotic debris. It also avoided further loss of valuable diagnostic material. An accurate diagnosis was rendered in 70 cases; that was not possible by LM alone. The whole procedure saves two to three hours of processing as centrifugation is not required after the agar embedding step. CONCLUSION: This technique was found to be cost- and time-effective, particularly suitable for developing countries, where financial resources are limited.

Borderline epithelial tumours of the ovary--a retrospective analysis of 31 cases.

Thirty one cases of epithelial borderline tumours of the ovary recorded over a period of six years were reviewed. The incidence of borderline tumours was 6% in relation to ovarian epithelial malignancies, with serous and mucinous types comprising three fourth of the lesions. The serous tumours were bilateral in 39%, revealed surface growth in 17% and had peritoneal implants in 11% of cases. The mucinous tumours were bilateral in 11% and had associated pseudomyxoma peritonei in 22% of cases. Nuclear grade appeared to correlate with extraovarian spread and surface growth in the serous borderline tumours, but not in the mucinous borderline tumours. The endometrioid borderline tumours and mixed epithelial borderline tumours were rare lesions. Twenty one patients (68%) presented in Stage-la. Surface growth correlated with recurrences. The prognosis remained good in serous borderline tumours even in the presence of implants as these were non-invasive. The mean disease free survival was 43.03 months. There was no statistical difference in disease free survival of patients with and without implants.

Calcifying epithelial odontogenic tumor: a clinico-radio-pathological dilemma.

The calcifying epithelial odontogenic tumor (CEOT) is a rare benign neoplasm of mandible in adults. The presentation of this entity is varied and often confused with a variety of mucosal and jaw lesions and clinical, radiological, and pathological feature of CEOT often-mimic malignancy. The objective of this report is to highlight the clinical features and radiological findings which should arouse suspicion of a benign lesion and importance of providing adequate clinical information to the pathologist to attain accurate diagnosis.We discussed two cases with tumors located in the maxilla. Both presented as expansile lesions with one biopsy proven squamous cell carcinoma. Both were pursued with clinico-radiological suspicion of benign lesions and confirmed with pathological correlation of histology and immunohistochemistry as CEOT. Therefore a High index of suspicion and clinico-radiological information are the key feature for diagnosis of this rare tumor.