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.

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.

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.

Oral squamous cell carcinoma arising in background of oral submucous fibrosis: a clinicopathologically distinct disease.

BACKGROUND: Oral cancer is the most common cancer in Indian males and is the third most common cancer in Indian females. Tobacco, alcohol, areca nut, and human papillomavirus (HPV) are the common etiologic factors. Each of these agents follows a unique model of carcinogenesis that leads to a certain distinct presentation and behavior. For example, HPV is strongly associated with oropharyngeal cancers in younger age and is known to have a better outcome and specific histopathologic characteristics. A high incidence of oral submucous fibrosis (OSMF) is linked to areca nut (group 1 human carcinogen) chewing in the Indian subcontinent. METHODS: We prospectively studied 371 consecutive patients with proven squamous cell carcinoma of the oral cavity. Of these, 112 patients had oral cancer with OSMF and 259 had oral cancer without OSMF. All patients underwent standard management and their clinicopathologic findings were recorded. RESULTS: We found that patients of oral cancer with OSMF are younger males with better prognostic factors such as better grade of tumor differentiation, lesser incidence of nodal metastases, and extracapsular spread. This difference was maintained even after matching for stage. We also report that presence of OSMF is an independent factor influencing nodal metastases. CONCLUSIONS: Based on these findings we propose that oral cancers with OSMF constitute a clinicopathologically distinct disease. Since all patients with OSMF had chewed areca nut with or without smokeless tobacco, we believe that the differences in the 2 groups emanate from differential mechanisms of areca nut carcinogenesis.

Natalizumab for moderate to severe Crohn's disease in clinical practice: the Mayo Clinic Rochester experience.

BACKGROUND: Not all patients with Crohn's disease (CD) respond or maintain response to anti-tumor necrosis factor (TNF) agents and alternative treatment is necessary. Natalizumab, a monoclonal antibody to alpha-4 integrin approved for CD, has demonstrated efficacy in randomized clinical trials. We describe our experience with natalizumab in clinical practice at Mayo Clinic Rochester. METHODS: Consecutive patients prescribed natalizumab for active CD were invited to participate and were followed prospectively. Incidence of infection, hospitalization, neoplasm, or other adverse events were recorded. Clinical activity was assessed using the Harvey-Bradshaw Index at each 30-day infusion visit. RESULTS: Between April 2008 and September 2010, 36 patients were prescribed natalizumab and 30 (83.3%) agreed to participate. Median disease duration was 9 years (range, 3-43). Twenty-three patients had prior exposure to two anti-TNF agents, seven to one agent. All patients experienced at least one adverse event; none of the 13 patients in whom natalizumab was stopped (43%) discontinued due to adverse events. Five patients had infusions held for infection. No patient developed progressive multifocal leukoencephalopathy (PML). Fourteen patients (46%) had clinical response. The cumulative probability of achieving complete response within 1 year was 56% (28%-73%). Four of seven patients were weaned off corticosteroids. CONCLUSIONS: In our experience with natalizumab in clinical practice, adverse events were manageable and did not result in treatment cessation. No PML cases were seen and clinical response was similar to that in clinical trials. Natalizumab results in clinical benefit in patients who have active disease and have failed anti-TNF therapy.

Minor salivary gland tumors of the oral cavity: a case series with review of literature.

BACKGROUND: Minor salivary gland tumors (MSGTs) are unusual, accounting for only 15-20% of all salivary gland tumors. The commonest site of MSGTs of the head and neck is oral cavity. AIMS: To describe our experience with MSGTs of oral cavity seen over a period of one decade and elucidate their prognostic factors. MATERIALS AND METHODS: Over a period of 10 years, from 1991 to 2000, all MSGTs of oral cavity were analyzed. All demographic, treatment and survival data were recorded. Kaplan-Meier curves were used to find the survival. Multivariate analysis was performed using Cox regression. RESULTS: We treated 104 patients with curative intent. The commonest site was hard palate, accounting for 54.8% of all sites. The commonest histology was adenoid cystic carcinoma (45.2%). There were 17 (16.34%) pleomorphic adenoma cases, while the remaining 87 (83.66%) were minor salivary gland malignancies. Treatment was surgical in 91.3% of patients. Adjuvant radiotherapy was administered in 38.5% of patients. The median follow-up was 50 months. Recurrences were seen in 22 (25.3%) of the 87 malignant cases. Using Kaplan-Meier analysis, the expected 10-year overall and disease-free survivals were 75.2 and 65.8%, respectively. Survivals were better in non-adenoid cystic tumors (non-ACC). On multivariate analysis, T status, tumor grade and adjuvant therapy were independent prognostic factors for disease-free survival. CONCLUSIONS: MSGTs of oral cavity have good overall survival despite recurrences. T stage, adjuvant radiotherapy and grade are independent prognostic factors for disease-free survival. Adenoid cystic tumors have worse outlook than non-ACC.

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.

Ocular biopsy through external needle drainage for isolated bilateral ocular relapse of childhood acute lymphoblastic leukemia.

BACKGROUND: Isolated ocular relapse of acute lymphoblastic leukemia is not commonly seen. Subretinal infiltration and exudative retinal detachment may not provide a positive vitreous biopsy for histopathologic confirmation. METHOD: We present a case of a 5-year-old male patient with acute lymphoblastic leukemia in remission, who presented with bilateral subretinal leukemic infiltrates and exudative retinal detachment. An ocular biopsy through external needle drainage histopathologically confirmed an ocular relapse of acute lymphoblastic leukemia. RESULTS: Isolated ophthalmic relapse of acute lymphoblastic leukemia can present as bilateral exudative retinal detachment with subretinal infiltration. CONCLUSION: External needle drainage of the subretinal fluid and subretinal infiltration can increase the diagnostic yield for histopathologic confirmation of the relapse.

Review article: understanding adherence to medication in ulcerative colitis - innovative thinking and evolving concepts.

BACKGROUND: Non-adherence to medication is an important challenge in the treatment of ulcerative colitis (UC). Epidemiological studies have demonstrated that non-adherence affects 40-60% of UC patients, and has a substantial impact on the course of the disease. In one study, non-adherence was associated with a five-fold increase in the risk of relapse. AIM: We review factors contributing to non-adherence to UC therapy, and emerging concepts in addressing the problem. METHODS: A search of the published literature on adherence to medication, combined with the authors' knowledge of the field. RESULTS: Adherence is a complex, multifactorial issue, with factors varying between patients and changing over time. Identifying patients at risk of non-adherence is a key first step in targeting interventions to improve adherence. However, investigations of single factors that affect adherence have provided conflicting evidence. Evaluating physical and perceptual barriers to adherence, and acknowledging the role of patients' beliefs and concerns regarding treatment provide valuable insights into the causes of non-adherence. This allows development of targeted interventions to improve adherence to UC therapy. Clinical tools to identify patients at risk of non-adherence are being developed to facilitate this approach. CONCLUSIONS: To help patients adhere better to maintenance therapy for UC, it is vital to consider patients' beliefs and concerns, and to evaluate and address both physical and perceptual barriers to adherence.

Sarcomatoid (spindle cell) carcinoma of the head and neck mucosal region: a clinicopathologic review of 103 cases from a tertiary referral cancer centre.

Sarcomatoid carcinomas are biphasic tumors proven to be monoclonal dedifferentiated forms of conventional squamous carcinomas. This study evaluates their clinicopathologic characteristics in head and neck mucosal sites and the problems in distinguishing them from other spindle cell tumors. A total of 103 cases with a confirmed diagnosis of sarcomatoid carcinoma accessioned in the pathology department of a tertiary referral cancer centre over a period of 7 years (2004-2010) were studied. An algorithm used for their diagnosis is presented. Ages of the patients were 22-90 years (median 53 years), and male:female ratio was 3.7:1. Site distribution was oral cavity (n = 65, 63.1%), larynx (18, 17.5%), oropharynx/hypopharynx (12, 10.7%), maxilla (6, 5.8%) and metastatic nodes (2, 1.9%). A large number of patients (95%) presented with a mass lesion of less than 1 year duration. Histopathologically, epithelial differentiation was evident on morphology in 48 (46.6%) cases, only on IHC in 34 (33%) cases, and in 21 (20.4%) no epithelial differentiation was seen. Typically, tumors were polypoidal (92, 89.3%) and ulcerated (95, 92.2%) with cells arranged predominantly in fascicles (59, 57.3%) or storiform pattern (17, 16.5%) amidst collagenous (50, 48.5%) or myxoid matrix (35, 34%). Anaplasia (2+/3+) and mitosis >10 per 10 HPF were noted in 96 (93.2%) cases. IHC was done in 82 cases; 55 (66.7%) showed positivity for epithelial markers with aberrant expression of mesenchymal markers in 43 (41.7%). Diagnosis of sarcomatoid squamous carcinoma is challenging because of overlapping histopathological features with other spindle cell tumors. Understanding their clinicopathologic characteristics facilitates their diagnosis and appropriate clinical management.

"Signet-ring" cells--a caveat in the diagnosis of a diffuse peritoneal mesothelioma occurring in a lady presenting with recurrent ascites: an unusual case report.

A diffuse peritoneal mesothelioma is a rare tumor. Exfoliative cytology forms the first step in the diagnosis of mesothelioma, since most of these cases presented with effusion. Despite well established cytomorphological features, a challenge exists in differentiating mesothelial cells, including reactive and malignant types from carcinoma cells and macrophages. Presence of "signet-ring" cells increases the diagnostic challenge as these can be forms of benign and malignant cells. Ancillary techniques like immunohistochemical (IHC) markers and ultrastructural analysis form useful adjunct in substantiating exact diagnosis. We report an unusual case study of a diffuse peritoneal mesothelioma in a 57-years-old lady, with no history of asbestos exposure, presenting with recurrent ascites, diagnosed on ascitic fluid cytology and on histology as an adenocarcinoma, based upon the presence of "signet-ring" cells. On review, clinicopathological correlation with IHC was helpful in forming correct diagnosis.

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.

Extraconal orbital tumors in children--a spectrum.

Orbital masses in children are uncommon but extremely challenging problems for clinicians and pathologists due to their critical location and availability of limited diagnostic material. We analyzed 47 specimens comprising biopsies, excision specimens, and FNAC of extraconal pediatric orbital masses (excluding retinoblastoma) accessioned in the pathology department over 5 years in a tertiary referral cancer center. Immunohistochemistry (IHC-74%) and molecular methods (one case) were done where necessary. The chief presenting symptom was proptosis in 55.3% patients and radiologically 53.8% malignant tumors showed extraorbital extension. A diagnostic algorithm was formulated to assess which cases needed pathology evaluation. Malignant round cell tumors (76.6%), chiefly embryonal rhabdomyosarcoma (51%), benign spindle cell neoplasms, and infectious lesions (tuberculosis, fungal infections), were seen. Of the malignant tumors, those confined to the orbit achieved good treatment response and had an event-free follow-up while those with extraorbital spread had poor outcome. Pediatric orbital masses range from completely treatable infectious lesions, surgically resectable benign neoplasms to aggressive malignancies requiring chemotherapy and radiotherapy. Pathologists play a key role in distinguishing these on small biopsy material and expediating accurate treatment thus saving the vision or life of a patient.

Predictors of persistence with 5-aminosalicylic acid therapy for ulcerative colitis.

BACKGROUND: Individuals with ulcerative colitis (UC) are at risk for poor persistence with therapy. AIM: To identify factors predicting persistence with 5-aminosalicylic acid (5-ASA) therapy after 3 and 12 months in subjects with UC. METHODS: In this retrospective cohort study, persistence with 5-ASA therapy was determined from prescription refill data from a commercial health insurance claims database. The analysis included subjects with UC who filled a prescription for any oral 5-ASA between October 2002 and September 2004. Persistence was defined as prescription refill at 3 and/or 12 months. Multivariate logistic regression modelling identified variables independently associated with persistence at 3 and 12 months. RESULTS: In all, 3574 subjects were identified. Fifty-seven per cent (2044) were persistent at 3 months. Glucocorticoid use before the index prescription predicted improved persistence at 3 months. Psychiatric diagnosis, mail order of the index prescription, female gender and co-pay predicted decreased persistence. At 12 months, 1124 (55%) remained persistent. Rectal 5-ASA use, older age and switching to a different 5-ASA predicted improved persistence at 12 months. Hospitalization for a gastrointestinal condition, mail order of the 3-month prescription and number of co-morbid illnesses predicted lower persistence. CONCLUSION: Persistence with 5-ASA treatment in UC is complex and multifactorial, and differs by time period.

Systematic review: impact of non-adherence to 5-aminosalicylic acid products on the frequency and cost of ulcerative colitis flares.

BACKGROUND: Ulcerative colitis (UC) can be maintained in remission with 5-aminosalicylic acid (5-ASA) medications, but frequent non-adherence by patients who are feeling well has been associated with more frequent flares of colitis. AIM: To perform a systematic review of the published literature and unpublished randomized clinical trials (RCTs) regarding the impact of non-adherence with 5-ASA medications on the incidence of UC flares and costs of care. METHODS: A search of MEDLINE, EMBASE and the Cochrane databases was performed. Prospective studies of UC maintenance with 5-ASAs in adults were selected if they included data on adherence and disease flares. Studies using insurance claims data to estimate the impact of non-adherence on cost of care were included. Data from unpublished RCTs were obtained from the FDA with a request under the Freedom of Information Act. RESULTS: The relative risk for flare in non-adherent vs. adherent patients ranged from 3.65 to infinity. Data were obtained from six unpublished 5-ASA RCTs, but none measured the impact of adherence on disease activity. The comorbidity-adjusted annual costs of care in adherent patients were 12.5% less than in non-adherent patients, despite increased medication expenditures. CONCLUSIONS: A substantial proportion of UC flares and medical costs of UC are attributable to 5-ASA non-adherence. As non-adherence to 5-ASA medications is common, cost-effective strategies to improve adherence are needed. The impact of adherence on disease activity should be measured in RCTs of all inflammatory bowel disease treatments.

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.