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.     

A suggested clinical score to predict the severity of adenoid obstruction in children

Chronic nasal obstruction in children is a very common disorder. Obstructing adenoid is usually the first to blame. Though the clinical assessment is essential, it is often considered unreliable or insufficient. We conducted a prospective clinical study to validate a clinical score predicting the severity of adenoid obstruction in symptomatic children. The clinical score (CS) included mouth breathing, snoring, restless sleep, frequent waking-up at night and obstructive breathing during sleep. Each item received a score of 0 or 1. The palatal airway was evaluated on a lateral nasopharyngeal x-ray. The degree of obstruction was assessed intra-operatively by a laryngeal mirror using a 3-grade scale. The volume of each adenoid specimen was measured. Eighty-six patients were enrolled, 51 boys and 35 girls, aged 13–181 months (mean 52, median 45). The CS correlated very well with the intra-operative findings (p < 0.01) and with the degree of palatal airway obstruction (p < 0.05) but not with the volume of the adenoid removed (p > 0.05). The CS was higher in children younger than 3 years (CS > 3 in 85.7% vs. 29.2%), having more frequent obstructive breathing during sleep (71.43% vs. 21.54%). A CS of three or higher, predicted severe obstruction in 96.5% of patients, as detected intra-operatively. The suggested CS is simple to use and is highly reliable in identifying children in need for adenoidectomy, in the context of normal anterior rhinoscopy and tonsils less than grade three.This work was presented at the podium of the XVIII IFOS in Rome, Italy on June 26, 2005.     

Contraction of scar tissue in the rabbit vitreous

Sheets of vitreous membrane (scar tissue) and associated retinal detachment were produced in the right eye of 86 adult New Zealand white rabbits by intravitreal injection of cultured autologous skin fibroblasts. The membranes were examined by light and electron microscopy and time-lapse cinephotomicrography. Immunohistochemistry was used to demonstrate alterations in the distribution of cytoplasmic contractile proteins. While retinal detachment and membrane contraction were taking place, there was pronounced increase in the numbers of fibroblasts with an elongated spindle shape. These spindle-shaped cells had some similarities to myofibroblasts including the presence of 'stress cables'. However, the myofibroblast-like cells stained much less avidly for cytoplasmic (actin) microfilaments than migratory fibroblasts seen at early stages of membrane development. The significance of migrating fibroblasts and myofibroblasts in scar contraction is discussed.     

The expression of 5T4 antigen in colorectal and gastric carcinoma.

The expression of 5T4, an oncotrophoblast cell surface antigen was examined in 72 colorectal and 27 gastric carcinomas, with immunoperoxidase technique, on frozen sections. Highly significant association was found between 5T4 expression in the malignant cells and metastatic spread. The results suggest that the appearance of 5T4 molecules in cancer cells reflects a change which may contribute to the development of metastatic potential.     

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.