Anaplastic thyroid carcinoma: diagnostic challenges,histopathologic features and ancillary testing

Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid malignancy with high mortality rate. This malignancy arises in thyroid follicular cells either denovo or with an associated differentiated thyroid carcinoma component. Clinically, it usually presents as a rapidly enlarging mass, pain and locally compressive symptoms. Histopathologic variability and heterogeneity often pose diagnostic challenges, especially in scant and paucicellular specimens. This article describes the clinical, histopathologic and molecular features of ATC and also addresses the associated diagnostic limitations and challenges.     

Molecular detection of Orientia tsutsugamushi strains circulating in Nagaland

The antigenic heterogeneity of Orientia in India is still unknown in many disease endemic areas. The present study aims to characterize the strains of O. tsutsugamushi circulating in Nagaland, Northeast India. Two patients clinically diagnosed with ST and hospitalized in Mon district hospital, Nagaland were identified from whom eschar tissues were collected. Both patients demonstrated antibodies against O. tsutsugamushi along with positive PCR amplification for 56 ?kDa gene. The prototype strain TA763 shared 90.4% homology with the sequences. Both the sequences formed a distinctive cluster demonstrating 100% similarity with strains identified from Thailand, Vietnam, China and southern parts of India.     

Galectin-3, fibronectin-1, CITED-1, HBME1 and cytokeratin-19 immunohistochemistry is useful for the differential diagnosis of thyroid tumors.

The diagnosis of thyroid tumors is critical for clinical management; however, tumors with follicular architecture often present problems. We evaluated the diagnostic use of the protein expression of four genes that were found to be upregulated in papillary thyroid carcinoma compared to normal thyroid (LGALS3, FN1, CITED1 and KRT19), and of the mesothelial cell surface protein recognized by monoclonal antibody HBME1 in thyroid tumors. Tissues from 85 carcinomas (67 papillary, six follicular, eight Hürthle cell and four anaplastic) and 21 adenomas were evaluated by immunohistochemistry for the expression of these gene protein products, for example, galectin-3 (GAL3), fibronectin-1 (FN1), CITED1, cytokeratin-19 (CK19) and HBME1. Non-neoplastic thyroids (29 adenomatous and 14 thyrotoxic hyperplasia, and 59 normal) were also studied. The expression of all five proteins was significantly associated with malignancy, and highly specific (> or = 90%) for carcinoma compared to adenoma. GAL3, FN1 and/or HBME1 expression was seen in 100% of carcinomas (85/85) and in 24% of adenomas (5/21). Coexpression of multiple proteins was seen in 95% of carcinomas and only 5% of adenomas (P<0.0001). Coexpression of FN1 and GAL3 (FN1+ GAL3+, 70/85) or FN1 and HBME1 (FN1+ HBME1+, 53/85) was restricted to carcinomas, while their concurrent absence (FN1- GAL3- or FN1- HBME1-, 18/21 adenoma) was highly specific (96%) for benign lesions. Among non-neoplastic thyroids, adenomatous hyperplasia frequently expressed GAL3 (n=16), CK19 (n=9) and CITED1 (n=7), but the expression was predominantly focal in contrast to the diffuse expression in carcinomas. An immunohistochemical panel consisting of GAL3, FN1 and HBME1 may be useful in the diagnosis of follicular cell-derived thyroid tumors.     

Sequence Analysis of the RNA Polymerase Gene of Foot-and-Mouth Disease Virus Serotype Asia1

The complete nucleotide (nt.) sequence of the RNA polymerase (3D) gene and 81 nt. in the 3-untranslated region of foot-and-mouth disease virus (FMDV) serotype Asia1 (IND63/72) was determined and compared with the sequence of other FMDV serotypes. The 3D genomic region was 1410 nt. long encoding 470 amino acids with an inframe stop codon (TAA) at nt. position 1411–1413. The deduced amino acid sequence of the protein showed 8 conserved motifs as reported in other picornaviruses, 2 of which are 100% identical across the serotypes. Antigenic regions in the polymerase protein were predicted and found to be located at the N-terminus of the protein. The phylogenetic analysis showed that the FMD viruses were segregated into different clusters based on geographical origin; the Asia1 virus did not cluster tightly with any of the geographical groups.     

Carcinoid tumors of the lung: a diagnostic challenge in bronchial washings

Bronchial washings are used routinely in the diagnosis of lung tumors. However, unlike other tumors, the diagnosis of bronchial carcinoids on bronchial washings is difficult. We reviewed 17 cases of histologically proven bronchial carcinoids from the files of the cytology laboratory over a period of 15 yr (1986–2001). The bronchial washings and histology sections of all the cases were reviewed separately by two independent observers and the results tabulated. Two cases had inadequate bronchial washings for evaluation and were excluded from the study. A growth was identified on bronchoscopy in 13 of 15 cases. Initial cytologic diagnoses were ?adenocarcinoma/?carcinoid and suspicious of carcinoid in one case each. However, on review, tumor was identified in 10 of 13 cases initially considered to be negative. The possible reasons for a false‐negative report on initial cytology include the paucity of tumor cell fragments in the bronchial washings (5 of 12 cases showing only one to two tumor fragments) and their bland appearance, often being mistaken for benign columnar cells. This study highlights the potential pitfalls in the diagnosis of bronchial carcinoids on bronchial washings and underlines the importance of a diligent search in cases with high clinical suspicion and positive bronchoscopic findings. Diagn. Cytopathol. 2004;30:62–66. © 2004 Wiley‐Liss, Inc.     

Luteolin promotes mitochondrial protection during acute and chronic periods of isoproterenol induced myocardial infarction in rats

ObjectiveAn attempt has been made to evaluate the mitochondrial protection in acute and chronic periods after isoproterenol (ISO)-induced myocardial-infarction (MI) in male Wistar rats.Materials and methodsLuteolin was supplemented by intra-gastric intubation at a daily dose of 0.3 mg/kg body weight for 30 days. In the acute MI model, luteolin had been administered once per day to rat groups during 30 days. On 29th and 30th days, the rats of the acute MI control groups were administered 85 mg/kg body weight, isoproterenol, intra-peritoneally at an interval of 24 h. In the chronic MI model luteolin was supplemented to the rat group during 30 days. On the 1st and 2nd days, the rats of the chronic MI control and luteolin treatment groups were administered ISO by the same way.ResultsThe isoproterenol-treated rats both in acute and chronic models showed an increase in the level of TBARS and a decrease in the activities of mitochondrial antioxidants in MI rats, an increase in levels of mitochondrial lipid profile except phospholipids and the activities of mitochondrial enzymes were decreased in isoproterenol-treated rats. Oral treatments with luteolin in both acute and chronic models showed a significant decrease in the levels of mitochondrial lipid peroxidation, increase in the mitochondrial antioxidant levels and also decrease in the mitochondrial enzymes.ConclusionThus the present study revealed that luteolin ameliorates mitochondrial damage in isoproterenol induced myocardial infarction by maintaining lipid peroxidation metabolism due to its free radical scavenging, mitochondrial lipids, antioxidants and mitochondrial enzymes. Histopathological observations were also in correlation with the biochemical parameters.