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Influence of splenectomy on hemostasis in agnogenic myeloid metaplasia.

The effect of splenectomy on hemostatic tests was studied in 10 patients with agnogenic myeloid metaplasia. Prolonged partial thromboplastin time and abnormal prothrombin consumption were found before splenectomy and were normalized postoperatively in the majority of patients. Prolonged bleeding time and prothrombin time were normalized in some patients. While platelet counts and fibrinogen levels rose significantly following splenectomy, platelet aggregation remained impaired. Thrombocytosis and increased fibrinogen level after splenectomy in patients with agnogenic myeloid metaplasia can enhance a thromboembolic tendency.

Adult↗

Evolution of malignant lymphoma in agnogenic myeloid metaplasia.

Two young arab patients are described in whom malignant lymphoma developed within less than 1 year of the diagnosis of agnogenic myeloid metaplasia. Both patients showed a satisfactory response to combined chemotherapy. One of them died of hepatitis B at 10 months and the other is alive and in clinical remission 25 months after initial diagnosis. These observations demonstrate the close relation between myeloproliferative and lymphoproliferative syndromes and illustrate the diversity of malignant lymphoproliferative disorders into which agnogenic myeloid metaplasia may evolve in the course of disease. Our experience also demonstrates the ease with which some patients with an 'end stage' myeloproliferative disorder may respond to standard chemotherapy designed for the treatment of malignant lymphoma.

Adult↗

Lectin histochemistry on squamous metaplasia in different epithelial tumors of dogs.

Biotinylated lectins and avidin-biotin-peroxidase complex were used to study the correlation between cellular glycoconjugates' expression and squamous maturation in normal canine skin and in various epithelial neoplasms. Normal skin tissue was obtained from five, male, random-source dogs, 5 to 7 years old. The tumors tested, selected from the files of our Department, were fifteen squamous cell carcinomas from different tissue origin, five hepatoid perianal gland adenocarcinomas with squamous metaplasia, and fourteen solid mammary carcinomas with and without histologic evidence of squamous metaplasia. Except for mammary gland carcinomas, all tumors had been surgically excised from male dogs. Intermediate filament aggregation of twelve solid mammary gland carcinomas were studied electron microscopically. The basal and the lower spinous cells in normal skin and the less differentiated cells in squamous cell carcinomas stained moderately with Griffonia simplicifolia agglutinin-I. Spinous and granular cell layers stained strongly with Phytolacca americana mitogen and Arachis hypogaea agglutinin. Both lectins stained well-differentiated cells in squamous cell carcinomas. The electron microscopic study carried out in solid carcinomas of mammary glands revealed some relationship between the presence of intracytoplasmic tonofibrils and the binding of Griffonia simplicifolia agglutinin-I and Phytolacca americana mitogen to the tumors tested. Our results suggest that the glycosylation pattern occurring during normal keratinocyte differentiation is conserved in squamous cell carcinomas and that Griffonia simplicifolia agglutinin-I and Phytolacca americana mitogen may represent useful tools in distinguishing poorly differentiated squamous cell carcinomas from other poorly differentiated mammary epithelial tumors.

Adenocarcinoma↗

IL-8 and its CXCR1 and CXCR2 receptors participate in the control of megakaryocytic proliferation, differentiation, and ploidy in myeloid metaplasia with myelofibrosis.

Myeloproliferation, myelofibrosis, and neoangiogenesis are the 3 major intrinsic pathophysiologic features of myeloid metaplasia with myelofibrosis (MMM). The myeloproliferation is characterized by an increased number of circulating CD34+ progenitors with the prominent amplification of dystrophic megakaryocytic (MK) cells and myeloid metaplasia in the spleen and liver. The various biologic activities of interleukin 8 (IL-8) in hematopoietic progenitor proliferation and mobilization as well as in neoangiogenesis prompted us to analyze its potential role in MMM. We showed that the level of IL-8 chemokine is significantly increased in the serum of patients and that various hematopoietic cells, including platelets, participate in its production. In vitro inhibition of autocrine IL-8 expressed by CD34+ cells with either a neutralizing or an antisense anti-IL-8 treatment increases the proliferation of MMM CD34(+)-derived cells and stimulates their MK differentiation. Moreover, addition of neutralizing anti-IL-8 receptor (CXC chemokine receptor 1 [CXCR1] or 2 [CXCR2]) antibodies to MMM CD34+ cells cultured under MK liquid culture conditions increases the proliferation and differentiation of MMM CD41+ MK cells and restores their polyploidization. Our results suggest that IL-8 and its receptors participate in the altered MK growth that features MMM and open new therapeutic prospects for this still incurable disease.

Aged↗

High levels of circulating CD34 cells, dacrocytes, clonal hematopoiesis, and JAK2 mutation differentiate myelofibrosis with myeloid metaplasia from secondary myelofibrosis associated with pulmonary hypertension.

We studied 25 patients with myelofibrosis with myeloid metaplasia and 19 patients with secondary myelofibrosis associated with pulmonary hypertension (PH). In these 2 groups, we compared the peripheral-blood CD34 count, the clonality of granulocytes and platelets in peripheral blood, the mutational status of the JAK2 kinase gene, and the morphology of the peripheral blood and bone marrow. We found that the following were distinctive features of myelofibrosis with myeloid metaplasia but not of secondary myelofibrosis due to PH: high circulating CD34 cell count, the presence of clonal platelets and granulocytes and of peripheral-blood dacrocytes, and a JAK2 1849G>T (V617F) mutation. We conclude that these are intrinsic features of clonal progenitors present in patients with myelofibrosis due to myeloproliferative disorders and that these features are not due to the abnormal marrow architecture seen in secondary myelofibrosis.

Adult↗

Colonic Paneth cell metaplasia is pre-neoplastic condition of colonic cancer or not?

ABSTRACTS: BACKGROUND: The carcinogenesis of colorectal cancer has been accepted by a model for a cascade of genetic alterations, named the adenoma-carcinoma sequence. In order to elucidate the carcinogenesis of the colorectal cancer more clearly, the genetic abnormalies of the non-neoplastic mucosal epithelium of the colon and rectum should be investigated. It has been speculated that colonic Paneth cell metaplasia (PaM) is one of the pre-neoplastic mucosa of colonic cancer. Therefore, we studied the propria mucosa of the right colon with PaM from the standpoints of the frequency of the K-ras codon 12 mutations (K-ras), which is initial genetic abnormality in colorectal cancer, and the loss of heterozygosity of microsatellite markers (LOH-MS), which has a relationship to development of colorectal cancer. METHODS: Fifty-two regions with PaM histopathologically from 12 surgically resected right colon specimens were studied. DNA extraction of the colonic mucosa with PaM was obtained using a microdissection method, and the frequency of the K-ras of PaM was investigated by enriched polymerase chain reaction-enzyme linked mini-sequence assay, and the frequency of the LOH-MS (D2S123, D17S250 and D5S346) of PaM was examined by high resolution fluorescenced labeled PCR primers. RESULTS: K-ras mutation was detected in fifteen regions among 52 PaM (28.9%). All mutations were a single mutation and GGT changed to AGT in eleven and GAT in four. LOH-MS were detected in twenty-one regions among 52 PaM (40.4%) (D2S123: 35.4%, 17/48 regions, D17S250: 13.7%, 7/51 regions, and D5S346: 0%, 0/52 regions). No K-ras mutations and LOH-MS were detected in the controls (Colorectal mucosa with no PaM). CONCLUSIONS: Colonic mucosa with Paneth cell metaplasia may be one of the pre-neoplastic mucosa in the development of the colonic epithelial neoplasia.

Journal Article↗

Changing pattern of cytokeratin 7 and 20 expression from normal epithelium to intestinal metaplasia of the gastric mucosa and gastroesophageal junction.

It is currently unclear whether intestinal metaplasia at the esophagogastric junction and in the distal esophagus represent a continuum of the same underlying disease process, i.e., gastroesophageal reflux, or constitute different entities with a different pathogenesis. Biopsies below the Z line might show specialized epithelium in some patients and the question is whether this is another form of short segment Barrett's esophagus or whether it is related to a generalized atrophic process of the stomach. Data from recent studies regarding the expression of cytokeratin CK7 and CK20 in intestinal metaplasia (IM) found at the gastroesophageal junction are conflicting. Prompted by these data we undertook the present study: a) to evaluate the expression of CK7 and CK20 in IM of the gastric cardia and to compare the findings with those in patients with Barrett's esophagus and IM of the gastric corpus and antrum mucosa; and b) to evaluate the immunophenotype of non-intestinalized cardiac mucosa and to compare it with that of normal gastric epithelium. We studied the expression of CK7 and CK20 on biopsy specimens from patients with long-segment Barrett's esophagus (n=17) and surgical resection and biopsy specimens of gastric cardia (n=15), corpus (n=14) and antrum (n=22) from patients with histological evidence of IM. Eighty-four biopsy specimens from 42 patients (antrum n=15, corpus n=20, cardia n=7) without evidence of IM were studied as a control group. We observed an immunophenotype characterised by diffuse moderate to strong CK7 staining on the surface and crypt epithelium combined with strong CK20 staining on the surface and superficial part of the crypts in 94.1% (16/17) of the cases with long-segment Barrett's esophagus, but in none of the 36 cases with IM in distal stomach (antrum and corpus). IM in the gastric cardia expressed the immunophenotype seen in IM of the gastric mucosa in 93.3% (14/15) of the cases. On the other hand, normal cardiac epithelium expressed patchy strong CK7 staining on the surface epithelium and on both, superficial and deep parts of the pits combined with patchy strong CK20 staining on the surface epithelium and superficial pits, a feature permitting distinction of the normal cardiac epithelium from those of the normal gastric antrum and corpus epithelium. We conclude that the expression of cytokeratins 7 and 20 can be used to distinguish the origin of IM of the gastroesophageal junction. The CK7/20 immunophenotype of IM in the gastric cardia closely resembles that of the IM in the gastric antrum and corpus and is different from IM in long-segment Barrett's esophagus. In contrast, the CK7/20 immunophenotype of the cardiac epithelium is different from that of the gastric antrum and corpus mucosa, suggesting that cardiac epithelium might not be a native normal gastric epithelium but one that is acquired as a consequence of longstanding inflammation. Changing pattern of CK7 and CK20 expression from normal to intestinalized epithelium suggests that IM arising from cardiac epithelium might have distinctive features.

Barrett Esophagus↗

Spindle cell metaplasia in follicular adenoma of the thyroid gland: case report and review of the literature.

Spindle cell tumors and reactive proliferations of the thyroid gland are rarely reported. In this report, we described a case of follicular adenoma with spindle cell component. The spindle cell proliferation constituted more than 90% of the 4.0 cm lesion and showed fascicular pattern with focal areas of collagenous stroma and hyalinized blood vessels. There was a transition from follicle like glandular structure to fascicular pattern. There was no mitosis and necrosis. Immunoreactivity with thyroglobulin proved that the spindle cell proliferation is of follicular origin. Also strong thyroglobulin and cytokeratin positivity of glandular areas and the gradual decrease in positivity of spindle cells showed epithelial-mesenchymal transformation/spindle cell metaplasia of the thyroid. We thought that it is important to differentiate spindle cell metaplasia in follicular lesions, especially follicular adenoma, from malignant thyroid neoplasms.

Adenoma↗

Endoprevention of esophageal cancer: endoscopic ablation of Barrett's metaplasia and dysplasia.

This review describes the use of endoscopic therapy for the treatment of Barrett's disease and the prevention of esophageal carcinoma, predominantly a disease of older white men. While the term endoprevention may be novel, gastroenterologists have been using endoscopic techniques to prevent colon cancer for decades. For the endoprevention of Barrett's carcinoma, the regulatory approval for the use of porfimer sodium photodynamic therapy was an important milestone, as this treatment has been proven to safely ablate Barrett's glandular epithelium, including high-grade dysplasia, and significantly decrease the risk for the development of invasive cancer in several single-center studies, a prospective multicenter randomized controlled study using expert centralized histopathology analysis and long-term single-center results. Newer methods of mucosal ablation, such as the radiofrequency balloon, have been developed for the treatment of patients with Barrett's metaplasia or dysplasia. These newly developed techniques are able to treat large fields of glandular epithelium in a short treatment procedure using safe, effective, durable methods for the complete ablation of Barrett's metaplasia and low-grade dysplasia. These techniques may finally allow the interventional gastrointestinal endoscopist to prevent the development of esophageal carcinoma, just as colonoscopy with polypectomy has prevented colon cancer. However, it will be critically important to document the safety, durability and efficacy of these devices. Ultimately, the impact of successful Barrett's ablation on the incidence of Barrett's carcinoma, and the need for postablation surveillance endoscopy must be determined.

Barrett Esophagus↗

Squamous metaplasia of the middle ear epithelium.

This study deals with the expression of cytokeratins (Cks) in squamous cell metaplastic lesions in rat and human middle ear. In rats, squamous metaplastic lesions could be induced during chronic otitis media. The histological features of these lesions were similar to those observed in the human middle ear. Immunohistochemistry revealed that squamous cell metaplasia in both rat and human middle ear is characterised by a loss of simple epithelial cell related Cks and the appearance of Cks characteristic of stratified and cornifying epithelia. This indicates a true change in the differentiation of the middle ear epithelium. It is concluded that the Ck profile of the cholesteatoma matrix cannot be used as a variable to decide whether the origin of cholesteatomas is epidermal or metaplastic. This rat model is suitable for studying squamous cell metaplasia in relation to cholesteatoma genesis.

Animals↗

[Squamous metaplasia of bulbar conjunctiva in the course of long-term topical antiglaucoma therapy].

PURPOSE: The aim of this study was to determine how long-term topical antiglaucoma treatment affects the bulbar conjunctiva. MATERIAL AND METHODS: 59 glaucoma patients and 30 healthy people were examined by the use of impression cytology for changes in bulbar conjunctiva. Patients with glaucoma were on stable regimen of one or two antiglaucoma drugs for a minimum 1 year. RESULTS: Squamous metaplasia of bulbar conjunctiva was found in 26.6% of patients treated with beta-blocker alone for 1-2 years and in 42.8% of patients treated with this drug for longer than 2 years. Similar changes were found in patients treated with beta-blocker with miotic--in 60% people who were on stable regimen for 1-2 years and in 70% treated longer than 2 years. No conjunctival changes were observed in healthy people. CONCLUSIONS: Long-term topical antiglaucoma medication may produce squamous metaplasia of bulbar conjunctiva.

Administration, Topical↗

Osseous metaplasia in a growth hormone-secreting pituitary adenoma.

A case of growth hormone-secreting adenoma of the pituitary gland showing osseous metaplasia is described in a 56-year-old acromegalic female. The tumor was composed of nests of densely granulated cells separated by and intermixed with calcifications, trabeculae of mature bone and fat. Calcifications are seldom found in pituitary adenomas. In rare instances, calcium deposits can be prominent enough to lead to the formation of pituitary stones and bone which replace the entire tumor mass. Analogously with metaplastic meningiomas, we propose using the term metaplastic adenoma to define cases with osseous metaplasia in order to distinguish between lesions containing bone from the more frequently seen calcified adenomas.

Acromegaly↗

Loss of Rh antigen associated with acquired Rh antibodies and a chromosome translocation in a patient with myeloid metaplasia.

Myeloid metaplasia is a clonal disease of the marrow pluripotent stem cell in which a constant cytogenetic abnormality could result in an altered antigenic characteristic of hematopoietic cells. A 57-yr-old man who had acquired myeloid metaplasia at age 37 was noted to be Rh negative, although blood typing at age 33 was Rh positive. His erythrocytes reacted with anti-c and anti-e, typical for an Rh negative individual. Analysis of 11 metaphase bone marrow cells by G-banding revealed 46 chromosomes with a consistent anomaly in 100% of cells involving chromosomes 1 and 13. The changes were consistent with a reciprocal translocation, with break points at approximately 1p32 and 13q22, although break points at 1p13 and 13q14 were also possible. Since previous cytogenetic data have localized the Rh gene to the short arm of chromosome 1, our data indicate the Rh gene lies within the segment u13 leads to 1p32. Serum of this patient had circulating anti-D and anti-C antibodies. Consequently, this patient lost immunologic tolerance to a "self antigen" after losing the ability to express this antigen.

Chromosome Mapping↗

Correlation between intestinal metaplasia of the gastric cardia and gastroesophageal reflux disease.

BACKGROUND/AIMS: IMC (intestinal metaplasia of the cardia) has been a subject of great interest, given the rapidly increasing incidence of adenocarcinoma in this location, over the past two decades. Whether this histological alteration is a consequence of gastroesophageal reflux disease, or a manifestation of an H. pylori-related multifocal atrophic gastritis, is unclear. Furthermore, whether IMC should be considered a premalignant lesion of gastric cardia is still unknown. We performed a prospective study in order to determine the prevalence of IMC in patients presenting for elective esophagogastric-duodenal endoscopy and to evaluate a potential association between IMC and some clinical, endoscopic and histological variables. METHODOLOGY: Biopsy specimens were taken from 105 unselected patients undergoing routine diagnostic endoscopy. Eight biopsies were taken from different sides, for histological evaluation: 1 above and 3 below the squamocolumnar junction, 2 from gastric fundus and 2 from gastric antrum. All specimens were stained with hematoxylin and eosin-Alcian blue and modified Giemsa to facilitate the detection of H. pylori. RESULTS: Eighty-six patients (50 males, 36 females) with a mean age of 46.5 years (range: 23-75 years), were included in the study. Twenty-one (24.5%) were found to have IMC; 4 (19%) of these had concomitant low-grade dysplasia of the cardiac mucosa. IMC was associated with: males (P = 0.04), endoscopic diagnosis of esophagitis (P = 0.02), histological diagnosis of esophagitis (P = 0.008), mucosa of the cardiac type (P = 0.02), chronic carditis (P = 0.002) and dysplasia (P = 0.04). There was no correlation with: age, reflux symptoms, activity of carditis, H. pylori infection of the cardia and intestinal metaplasia of the distal gastric mucosa. CONCLUSIONS: IMC is common in our area. It is associated with endoscopic and histological changes of gastroesophageal reflux disease, but not with H. pylori infection of the cardia. Although 19% of patients presented concomitant dysplasia (of low grade), long-term follow-up studies will be necessary to assess the effective risk of IMC for cancer transformation.

Adult↗

Polycythaemia after myeloid metaplasia with fibrosis: an unusual sequence.

In November 1981, a 77-yr-old woman consulted for myeloid metaplasia with fibrosis. A persistent hyperleucocytosis was treated with hydroxyurea from March, 1985 to March, 1989. At that time facial dyskinesia and polycythaemia developed. Investigations revealed a regression of myelofibrosis and a predominance of myeloid metaplasia in the liver. The mechanism of this event, rarely observed in myeloproliferative syndromes, is discussed in this new case.

Aged↗

Hematopoietic progenitor cells in a patient with myeloid metaplasia without myelofibrosis.

A rare case of myeloid metaplasia without myelofibrosis is presented. Findings that the increase in blood megakaryocyte progenitor cells was not as prominent as the increase in granulocyte-monocyte and erythroid progenitor cells, and that the increase in bone marrow megakaryocytes was only slight might explain the absence of bone marrow fibrosis in this case. However, it is not clear whether the disease is a subtype or merely an early stage of myelofibrosis with myeloid metaplasia.

Aged↗

Agnogenic myeloid metaplasia in an ovarian steroid cell tumor with virilization: a case report.

BACKGROUND: Extramedullary hematopoiesis in patients without hematologic disorders is very rare and has apparently never been described previously in association with an ovarian steroid cell tumor. CASE: An 18-year-old woman was admitted to our clinic due to primary amenorrhea. the On examination she had significant facial hirsutism, clitoromegaly and and Adam's apple. The serum level of testosterone was elevated. A 7-cm, right ovarian mass was enucleated during laparotomy. Histology revealed a steroid cell tumor with foci of myeloid metaplasia; bony trabecula formation was present. There was no evidence of hematologic or systemic disease. The hormone values became normal 1 month postoperatively. CONCLUSION: This report describes a patient with agnogenic myeloid metaplasia in an ovarian steroid cell tumor with virilization; this association was not previously reported.

Adolescent↗

[The morphological characteristics of cervical squamous metaplasia in reproductive women].

The aim of our study was to identify the morphological characteristics of cervical squamous metaplasia in reproductive women. We have performed the biopsy in patients who had the abnormal transformation zone by colposcopy. Cervical biopsies were studied histologically by HandE. The results showed that cervical squamous metaplasia has different clinical importance in reproductive patients. In reproductive women it is associated with cervical intraepithelial neoplasia. In reproductive women assessment of pseudoerosions has important meaning.

Adult↗