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P T Chandrasoma

Publications and source records attributed to P T Chandrasoma.

At least 19 recordsLinked to original sources
PubMed2006

Cdx-2 expression in squamous and metaplastic columnar epithelia of the esophagus.

The molecular pathogenesis of Barrett's esophagus is poorly understood. Evidence suggests that at a phenotypic level, the metaplastic process begins with the transformation of squamous epithelium in the distal esophagus to cardiac mucosa, which subsequently becomes intestinalized. The homeobox gene Cdx-2 has been shown to be an important transcriptional regulator of embryonic differentiation and maintenance of adult intestinal type epithelium. We hypothesized that Cdx-2 gene expression levels increase with the phenotypic transformation of normal squamous mucosa to the intestinalized columnar mucosa of Barrett's esophagus. Endoscopic biopsies were obtained at the gastroesophageal junction in patients with symptoms of gastroesophageal reflux disease and classified according to histology: normal squamous mucosa (n = 62), cardiac mucosa (n = 19), oxynto-cardiac mucosa (n = 14), and intestinal metaplasia (n = 15). Duodenal biopsies (n = 26) served as the columnar control. After laser capture microdissection and RNA isolation, gene expression levels of Cdx-2 were measured in each tissue type by quantitative reverse transcription polymerase chain reaction. Consistent with its known function, Cdx-2 gene expression levels were highest in duodenal mucosa and nearly absent in squamous epithelium. There was a stepwise increase in Cdx-2 gene expression from cardiac to Barrett's epithelium (P < 0.001). Expression levels of Cdx-2 in cardiac and oxynto-cardiac mucosa were 40-70 times higher and Barrett's mucosa 400 times higher than that found in squamous epithelium. Relative expression of the homeobox gene Cdx-2, known to induce differentiation of intestinal type epithelium, increases in a stepwise fashion during the phenotypic transformation of distal esophageal squamous mucosa to cardiac columnar mucosa and to the intestinalized columnar mucosa of Barrett's esophagus. Therefore, Cdx-2 may be a potential biomarker to detect the early transition to Barrett's esophagus.

Adolescent↗
PubMed2001

Distribution and significance of epithelial types in columnar-lined esophagus.

An abnormal columnar-lined esophagus (CLE) is characterized by the presence of cardiac mucosa (CM) oxynto-cardiac mucosa (OCM), and intestinal metaplastic epithelium (IM) between gastric oxyntic mucosa and esophageal squamous epithelium. Thirty-two patients with CLE measuring 2-16 cm long had 5-37 biopsies per patient that showed CM, OCM, or IM for a total of 424 biopsies. Detailed mapping of the distribution of epithelial types within the CLE showed a distinct zonation of epithelial types; CM was present throughout the CLE, whereas OCM and IM tended to occur in the distal and proximal part of the CLE, respectively. All 32 patients (64 of 68 biopsies) showed IM at the most proximal level, compared with 22 of 32 patients (40 of 102 biopsies) in the most distal level biopsies. The density of goblet cells was highest in the most proximal level. The differences in prevalence and density of goblet cells between most proximal and most distal level biopsies were highly significant. These data suggest that for a given number of biopsies within the CLE, the likelihood of finding IM is greatest when the biopsies are concentrated in the most proximal area of the CLE. We suggest that glandular transformation of squamous epithelium results in CM. which evolves into OCM and IM by development of specialized parietal cells and goblet cells, respectively. The severity and nature of reflux cause these epithelial transformations in a constant and predictable manner. Recognition of these changes permits the development of morphologic definitions of reflux disease and the characterization of the sequence of epithelial changes that represent the reflux-adenocarcinoma sequence.

Barrett Esophagus↗
PubMed2000

Definition of histopathologic changes in gastroesophageal reflux disease.

A series of 71 patients with multiple measured biopsies of the gastroesophageal junctional region permitting assessment of the presence and length of different glandular epithelial types is presented. All but nine of 53 patients in whom a 24-hour pH study was performed had abnormal reflux, suggesting that endoscopic recognition of an abnormal columnar mucosa at the gastroesophageal junction sufficient to precipitate multiple-level biopsies indicates a high probability of abnormal reflux. All patients had cardiac mucosa (CM) or oxyntocardiac mucosa (OCM). CM was present in 68 of 71 patients. The prevalence of intestinal metaplasia increased with increasing CM+OCM length, and was present in all 22 patients with a CM+OCM length >2 cm and in 20 of 49 patients with a CM+OCM length <2 cm. Patients with a CM+OCM length >2 cm had a markedly higher acid exposure than patients with a CM+OCM length <2 cm. The findings suggest that the presence of CM and OCM in the junctional region are predictive of abnormal acid exposure, and that increasing OCM+CM length correlates strongly with the amount of acid exposure. The histologic finding of CM and OCM represents a sensitive histologic criterion for gastroesophageal reflux rather than normal epithelia. These diagnostic criteria represent the first useful histologic definitions for assessing the presence and severity of reflux.

Gastric Mucosa↗
PubMed2000

Histology of the gastroesophageal junction: an autopsy study.

Current diagnostic criteria for reflux disease and Barrett's esophagus are based on the belief that the gastroesophageal junction normally contains 2 cm of cardiac mucosa composed of mucous glands devoid of parietal cells. This autopsy study disproves this belief. Even when the entire circumference of the gastroesophageal junction is examined, pure cardiac mucosa was completely absent in 56% of patients. All patients had oxyntocardiac mucosa, in which glands contained a mixture of mucous and parietal cells. Cardiac and oxyntocardiac mucosae were present only in part of the circumference of the junction in 50% of patients. The measured maximum length of cardiac plus oxyntocardiac mucosa was less than 0.5 cm in 76% of patients. There was a tendency for the presence and extent of cardiac mucosa to increase with age. Cardiac mucosa at the junction is therefore frequently absent, has considerable individual variation, is very small in extent when present, is commonly absent from some part of the circumference of the junction, and increases in prevalence and length with age. These characteristics of cardiac mucosa make it highly unlikely that it is a normal structure. We develop the hypothesis that cardiac mucosa represents an early histologic manifestation of gastroesophageal reflux.

Adolescent↗
PubMed1997

Presence of p53 mutations in primary nasopharyngeal carcinoma (NPC) in non-Asians of Los Angeles, California, a low-risk population for NPC.

Mutatins of the p53 tumor suppressor gene are rare in nasopharyngeal carcinoma (NPC) patients who reside in high-risk areas, such as Southeastern China. Among this high-risk group, a pre-existing infection with the EBV and consumption of Cantonese salted fish are closely associated with NPC. We investigated the prevalence of p53 mutations in 28 primary NPC specimens from white (including Hispanic) and African-American patients in Los Angeles, who are at low risk for NPC. Using PCR-based single-strand conformational polymorphism and direct sequencing, we found four mutations (14%) in exons 5-8 of the p53 gene in four patients. All were C-to-T transition mutations: two were present in exon 5-one at codon 142 [CCT (Pro)-->CTT (Leu)] and another at codon 144 [CAG (Gln)-->TAG (stop codon)]. The other two mutations were identified in exon 8: one at codon 273 [CGT (Arg)-->CAT (His)], a CpG site, and one at codon 271, a silent mutation [GAG (Glu)-->GAA (Glu)]. This is the first report investigating the presence of p53 missense mutations in NPC among a low-risk population. Our data indicate that p53 is also an infrequent event among NPC patients at low risk for the disease.

Adolescent↗
PubMed1994

Paragonimiasis in a cystic breast mass: case report and implications for examination of aspirated cyst fluids.

We report a case of paragonimiasis diagnosed by fine-needle aspiration of a breast mass in a middle-aged Korean female with a history of breast silicone injections. Although parasitoses have been discovered by aspiration of cyst fluid in otherwise sterile sites (i.e., liver and lung), the cystic presentation in the breast of a middle-aged female complicated the diagnosis in this case. Some authors have argued against the routine cytologic examination of nonbloody cyst fluids in premenopausal women, but this protocol may lead to a false negative diagnosis in the rare instance of a parasitic cyst. While microscopic examination of breast cyst fluid is probably not warranted in every patient, it may be useful in patients at risk for unusual cystic lesions, especially if clinical and mammographic signs of fibrocystic change are absent.

Adult↗
PubMed1994

Papillary adenocarcinoma of the rete testis: a case report and review of the literature.

Adenocarcinoma of the rete testis is a rare neoplasm with 40 reported cases in the world literature to our knowledge. Although the natural history of this tumor is not well known, it appears highly malignant even in localized forms. Adenocarcinoma of the rete testis is highly resistant to adjuvant radiotherapy and any known chemotherapeutic regimen. We recommend radical orchiectomy followed by a retroperitoneal lymphadenectomy as the treatment for clinically localized Stage A tumors and minimal or microscopic Stage B disease. We report a case of adenocarcinoma of the rete testis and review the world literature.

Adenocarcinoma, Papillary↗
PubMed1993

Sporadic visceral myopathy with inclusion bodies. A light-microscopic and ultrastructural study.

We report the clinical and pathologic findings of two patients with sporadic visceral myopathy. Both presented with chronic intestinal pseudo-obstruction that necessitated colectomy. Microscopically, typical changes of primary visceral myopathy were present, including variable fibrous replacement of the muscularis externa and vacuolar degeneration of myocytes. In addition, the muscle cells contained cytoplasmic inclusions that have only been recently reported in visceral myopathy. These inclusions were numerous and easily visible in routine hematoxylin-eosin-stained sections but greatly enhanced by periodic acid-Schiff staining. They were reactive immunohistochemically at their periphery and were seen to be myofibrils at various stages of degeneration on electron microscopy. Inclusions were present in both muscularis externae and muscularis mucosae and were identified in mucosal biopsy specimens, providing a means of diagnosing this type of myopathic change on endoscopic biopsies.

Adult↗
PubMed1993

Cerebrovascular histopathology after intracarotid infusion of Gelfoam in the rat.

To evaluate the histopathology of Gelfoam on the cerebral vasculature, 42 Sprague-Dawley rats weighing 250 to 300 g received internal carotid artery infusions of 0.3 ml of Gelfoam solution (5 mg/ml) or normal saline (0.9%). The animals were killed at 1 hour, 5 hours, 3 days, 1 week, 2 weeks, and 4 weeks after the infusion. The brains were removed, sectioned, and stained with hematoxylin and eosin. Examination of brain sections revealed Gelfoam emboli lodged primarily in the small leptomeningeal arteries. At 5 hours after infusion, inflammatory cells were noted in the arterial walls with vessel occlusion. Further canalization of vessels was noted at 1 week. At 4 weeks, Gelfoam was not seen in the specimens. This study suggests that Gelfoam acts as an embolic agent in vessels over short periods of time with no residual inflammatory activity postinfusion.

Animals↗
PubMed1992

Abdominal angiostrongyliasis mimicking acute appendicitis and Meckel's diverticulum: report of a case in the United States and review.

Two cases of children with abdominal angiostrongyliasis acquired within the United States are reported. The index patient presented with complaints consistent with appendicitis, but at surgery findings were thought to represent an atypical presentation of a Meckel's diverticulum. His sole sibling (sister) had eosinophilia, no other intestinal parasites on fecal examination, and a positive serologic test, all suggesting infection with Angiostrongylus costaricensis. Because infections with this parasite are not known to result from human-to-human transmission, his sister's infection represents a second case.

Acute Disease↗
PubMed1992

Meningeal melanocytoma: diagnostic criteria for a rare lesion.

A case of meningeal melanocytoma, the 14th in the literature, is presented. Neurodiagnostic imaging, with both computed tomographic scan and magnetic resonance imaging, is included. Pathological examination of the tumor consisted of light microscopy, electron microscopy, and immunohistochemistry. The literature is reviewed and pathological criteria are presented to distinguish meningeal melanocytoma from meningiomas containing melanin pigment and from malignant melanoma.

Adult↗
PubMed1991

Diagnosis of pulmonary blastoma by fine-needle aspiration biopsy: cytologic and immunocytochemical findings.

A preoperative diagnosis of pulmonary blastoma was established by fine-needle aspiration (FNA) cytology in a patient who presented with a pulmonary mass discovered incidentally on chest x-ray. At the time of computed tomography-guided FNA, an on-site preliminary diagnosis of poorly differentiated carcinoma was made after examination of a rapid hematoxylineosin (H&E)-stained smear. Malignant epithelial and stromal elements could be demonstrated on smears subsequently stained with the H&E, Papanicolaou, and Diff-Quik methods. The cell block preparation showed a distinctly biphasic malignant tumor with classic morphologic features of pulmonary blastoma. We present the clinical, cytologic, immunocytochemical, and histologic findings of this case and re-emphasize the valuable contribution of adequate cell block preparations to accurate diagnosis of fine-needle aspiration material.

Actins↗
PubMed1990

Recurrent intraparenchymal hemorrhages from angiographically occult vascular malformations.

Thirteen patients with recurrent hemorrhages from angiographically occult vascular malformations are presented. Recurrent hemorrhages were indicated by the exacerbation of neurological deficits, the appearance of a new neurological deficit, or the onset of acute severe headache confirmed by evidence of recent hemorrhage on either computerized tomography or magnetic resonance imaging. Persistent neurological deficits correlated with an increased number of recurrent hemorrhages and their location. The median time from initial hemorrhage to the first recurrent hemorrhage was 12 months and the second rebleed generally occurred much earlier, with a median time of 2 months after the first. Eight patients underwent surgery with total excision and favorable results. One patient with a large pontine lesion underwent partial excision and has had a progressing neurological deficit from recurrent hemorrhages. Histopathological review confirmed the excised lesions to be cavernous angiomas. The authors conclude that angiographically occult vascular malformations are not the benign entity they were previously thought to be, and that they are prone to cause recurrent hemorrhages and persistent neurological deficits. Surgery can be effective and relatively safe in removing these lesions even in eloquent areas of the brain, but the necessity of occasional incomplete removal must be recognized in order to avoid creating an unacceptable neurological outcome.

Adolescent↗
PubMed1990

Multiparameter flow cytometric analysis of neoplasms of the central nervous system: correlation of nuclear antigen p105 and DNA content with clinical behavior.

Analysis of the DNA content of various solid tumors and hematological malignancies may provide useful prognostic information. To date, however, there has been a striking lack of correlation between DNA content in neoplasms of the central nervous system and clinical behavior. Simultaneous quantitation of DNA content and proliferation-associated nuclear antigen (p105) by flow cytometry was performed on paraffin-embedded tissues representing three major groups of central nervous system neoplasms--1) 21 astrocytic tumors, 2) 13 pituitary tumors, and 3) 19 meningiomas--and the results were correlated with clinical behavior. All 4 well-differentiated gliomas were diploid, while 3 of 9 anaplastic astrocytomas and 1 of 8 glioblastomas had a demonstrable aneuploid peak. Three of 13 pituitary tumors had an identifiable aneuploid peak, while only 2 of 19 meningiomas had an aneuploid DNA content. Cell-cycle analysis of the malignant gliomas revealed a significantly higher proliferative index (PI, %S + G2M) compared with the well-differentiated astrocytomas (P less than 0.05). Within the subgroup of diploid anaplastic astrocytomas, however, extended patient survival appeared to be associated with a higher PI. For diploid pituitary adenomas, the PI was consistently lower in the 3 tumors that recurred than it was in the remaining 8 adenomas. Nuclear antigen quantitation of diploid tumors showed a wide range of p105 expression in G0G1 cells, suggesting that, within each tumor, the cells are heterogeneous with respect to proliferative activity. Aneuploid nuclei of glial tumors showed enhanced expression of p105 relative to diploid cells of the same specimen. In pituitary tumors, the median G2M/G0G1 fluorescence ratio for p105 was significantly higher (P less than 0.05) for the 3 diploid recurrent tumors than for those that did not recur. These data support the assumption that the aggressive clinical course of malignant glial neoplasms may be related to an abnormal DNA stemline and/or an alteration in cell proliferative activity. Cell cycle analysis and measurement of p105 by this technique may provide information useful from both a prognostic standpoint and in directing adjuvant therapy.

Adult↗
PubMed1989

Primary mucosal malignant melanoma: an immunohistochemical study of 12 cases with comparison to cutaneous and metastatic melanomas.

Immunohistochemical analysis of 40 formalin-fixed, paraffin-embedded malignant melanomas (12 primary mucosal, 16 primary cutaneous, and 12 metastatic cutaneous) was performed to study the possible differences in immunostaining profiles according to location. The majority of melanomas were reactive with a polyclonal antibody to S100 protein (P-S100; 85%), a monoclonal melanoma-specific antibody (HMB-45; 88%), and a monoclonal antibody to vimentin (90%), and there were no differences in staining profiles for these antibodies by anatomic location. In contrast, while 13 of 16 cutaneous melanomas (81%) and ten of 12 metastatic melanomas (83%) were reactive with a monoclonal antibody to S100 protein (MoAb-079), only five of 12 mucosal tumors (42%) showed positive staining for MoAb-079. Similarly, 14 cutaneous melanomas (88%) and 11 metastatic melanomas (92%) showed positive staining for neuron specific enolase (NSE), while only four mucosal melanomas (33%) were NSE-positive. Of the 40 melanomas, all but two were reactive with either P-S100, MoAb-079, or HMB-45. These findings suggest that MoAb-079 and NSE may be less sensitive markers than P-S100 and HMB-45 for routinely processed mucosal melanomas as compared with cutaneous and metastatic tumors.

Antibodies, Monoclonal↗
PubMed1989

Intermediate filament expression in astrocytic neoplasms.

Immunohistochemical analysis of 30 paraffin-embedded astrocytic neoplasms was performed to correlate the expression of intermediate filament proteins with histologic subtype. Each tumor was studied with monoclonal antibodies to keratin, vimentin, desmin, 200-kd neurofilament protein, and glial fibrillary acidic protein (GFAP). Immunoreactivity with the anti-keratin monoclonal antibodies AE1 and AE3 was demonstrated in 24 cases (80%) including 4 of 6 (66%) well-differentiated astrocytomas (WDAs), 10 of 12 (83%) anaplastic astrocytomas (ANAs), and 10 of 12 (83%) glioblastomas multiforme (GBMs). These cases were further studied with the monoclonal antikeratin antibodies 34 beta E12 and 34 beta H11. Of the 24 AE1/AE3-positive cases, 14 (58%) reacted with 34 beta E12. None of the cases was reactive with 34 beta H11. Vimentin expression was demonstrated in 24 cases (80%), including 2 of 6 (33%) WDAs, 11 of 12 (92%) ANAs, and 11 of 12 (92%) GBMs. Coexpression of keratin and vimentin was observed in 20 cases (67%), including 2 of 6 WDAs, 9 of 12 (75%) ANAs, and 9 of 12 (75%) GBMs. Immunoreactivity with GFAP antibody was present in all 30 (100%) cases, but none of the tumors was reactive with antibodies to desmin or 200-kd neurofilament protein. These findings demonstrate that expression of both keratin and vimentin intermediate filaments is common in astrocytic neoplasms regardless of histologic grade.

Astrocytoma↗