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Prognostic parameters in myeloid metaplasia: agnogenic versus postpolycythemic.

Thirty-nine patients with myelofibrosis and myeloid metaplasia were diagnosed and followed during the period 1955-74. Twenty-eight suffered from agnogenic myeloid metaplasia and 11 from myeloid metaplasia following polycythemia vera. In an attempt to compare the two groups and to define prognostic guidelines, an analysis of survival with respect to various clinical parameters was made. The median survival time of patients with agnogenic myeloid metaplasia was seven years as opposed to only 28 months for the poltpolycythemic group. Older age at diagnosis, a large spleen, or its rapid enlargement, anemia and leukocytosis, but not thrombocytopenia, had a marked negative effect on survival. The clinical condition of most patients was remarkably stable during the entire course of their disease. If a significant drop in hemoglobin occurred, it was sudden, and caused by gastrointestinal hemorrhage or the development of acute leukemia. No demonstrable effect of therapy on survival was found.

Adolescent↗

Cytologic correlates of papillary immature metaplasia (immature condyloma) of the cervix.

Papillary immature metaplasia (PIM) of the cervix (immature condyloma) is a variant of low-grade squamous intraepithelial lesions (LSIL). It is frequently associated with human papillomavirus (HPV) types 6 and 11. The purpose of this study was to characterize the cytologic changes associated with this lesion. We analyzed 10 cases of PIM from our files and reviewed the Papanicolaou smears taken proximate to the time of the biopsy. Four cases had either reactive epithelial changes (2 cases) or cytologic findings typical of low-grade SIL, with koilocytosis (2 cases). Six cases displayed a spectrum of metaplastic cells with varying maturation that ranged from atypical reactive cells to atypical immature metaplastic cells. Binucleation was common. Some cells exhibited features characteristic of SIL, although the degree of nuclear atypia generally was less than that associated with high-grade SIL. Papanicolaou smears from all cases were interpreted as atypical (ASCUS) metaplasia or low-grade SIL. Follow-up biopsy in one case revealed a PIM in association with a high-grade SIL, the latter undiagnosed by smear alone. PIM is a distinct histologic entity that can present with a spectrum of cytologic findings. Its recognition histologically can resolve some cytologic/histologic discrepancies. Confusion with an immature HSIL or atypical immature metaplasia can occur in some instances and the diagnosis of PIM by cytology alone is not recommended, unless the diagnosis is qualified.

Cervix Uteri↗

Squamous metaplasia in colorectal polyps.

Two cases of rectal polyps that showed foci of squamous metaplasia are reported. In one, the squamous metaplasia was observed in an area of intramucosal adenocarcinoma. This finding tends to reinforce the contention previously made by some authors that squamous metaplasia in colorectal polyps may represent the precursor of primary colorectal squamous cell carcinoma or colorectal adenocarcinoma with squamous components (adenoacanthoma or adenosquamous carcinoma).

Aged↗

Adenocarcinoma of the male urethra with associated nephrogenic metaplasia. Case report and review of the literature.

Nephrogenic metaplasia is an uncommon sequela of chronic bladder irritation. The case described herein represents the second reported in the bulbomembranous urethra of the male. Important questions are raised regarding the premalignant potential of nephrogenic metaplasia. A review of the literature on adenocarcinoma of the male urethra and also of nephrogenic metaplasia of the bladder and urethra is presented.

Adenocarcinoma↗

Nucleolar organizing regions in the operated rat stomach: relationship to metaplasia, dysplasia and carcinoma.

This study investigated the role of duodenogastric reflux in rats after antecolic gastrojejunostomy. At the end of the study, adenocarcinoma was present in 43 per cent, dysplasia in 14 per cent and intestinal metaplasia in 43 per cent of animals. No such changes were found in control rats. A technique for silver staining nucleolar organizing regions (AgNORs) was applied to these lesions and to the control group. The AgNOR count gradually increased from normal gastric mucosa to carcinoma. This technique demonstrated differences in AgNOR count between normal mucosa and other lesions (adenocarcinoma, dysplasia, intestinal metaplasia) (P < 0.001). There was, however, considerable overlap among adenocarcinoma, dysplasia and metaplasia (P > 0.1).

Animals↗

Changes in morphology and cell proliferation during vitamin A-induced mucous metaplasia of developing chick scale cultured in vitro.

Throughout the process of vitamin A (V-A)-induced mucous metaplasia of the scale epidermis of a 12-day chick embryo, changes in the activities of cell proliferation were investigated in reference to morphological changes. In both the control and V-A cultures after 5 days, a dynamic steady state was established among the stratified layers which differentiated into keratinizing epidermis during the first 7 days. In the control, cell proliferates within only the basal layer and the cell cycle time, except Tg2, increased during 30 days of culture. In the V-A culture, this tendency was reversed in each parameter between day 10 and day 13, when symptoms of mucous metaplasia became morphologically prominent. On day 13 in the V-A culture, superficial cornified cell layers were sloughed off as whole sheets and concurrently DNA synthesis was reactivated throughout the entire cell layers of the epithelium. The correlation between two of five cell cycle times (Tgc, Tg1, Ts, Tg2, Tm) was statistically treated as linear regression lines and gave highly significant coefficients in every case. The regression coefficients between Ts and Tgc and Ts and Tg1 in V-A culture are significantly (P less than 0.01) smaller than those in the control. It was found that V-A induced sequential alterations in mucous metaplasia with respect both to morphology and proliferation in the epidermis of the chick embryo.

Animals↗

Squamous metaplasia in the healing of chronic colonic ulcers of the rat.

Chronic ulcers of the rat colon were produced by a administering a 3 per cent. hydrogen peroxide enema. Twenty-three per cent. of the animals with chronic ulcers had areas of squamous metaplasia at the wound margins which in some cases covered the defect. Electron microscopy revealed some areas similar to epidermis with the four characteristic cell layers. The cells demonstrated many filaments, membrane-coated granules, keratohyalin granules and keratin. The cells were linked by complex of cytoplasmic bridges and frequent desmosomes. Basal cells often displayed large irregular nuclei with double nucleoli. Other areas demonstrated a grossly irregular surface with marked cellular pleomorphism and defects in the basement lamina. The incidence of squamous metaplasia and squamous-cell carcinoma in the colon of man is discussed. The ultrastructural characteristics of squamous metaplasia in the trachea and bronchi is recorded and compared with those of the colon. It is suggested that as neoplasia has been observed to follow experimental metaplastic lesions in the bronchus, a similar ocurrence could take place in the colon as the squamous cells exhibited similar characteristics.

Animals↗

Endocrine cells in intestinal metaplasia of the stomach.

In this study we have investigated the mucin profile and the endocrine cell population in gastric endoscopic biopsies from 22 patients affected by chronic gastritis and intestinal metaplasia and in five surgical specimens of stomachs removed because of intestinal-type carcinoma (4) or peptic ulcer (1). High iron diamine-Alcian blue (HID-Ab) staining and peptide immunocytochemistry (peroxidase anti-peroxidase technique) were used. Forty-one foci of intestinal metaplasia were detected, 15 produced sulphomucins and 26 sialomucins. Of the endocrine cells investigated, gastrin and somatostatin cells were the most frequently observed, while cholecystokinin, glucose-dependent insulinotropic peptide-, secretin- and enteroglucagon-containing cells were also found in the metaplastic areas, but less frequently. No significant correlation was found between the type of mucin and the types of endocrine cells present, the latter usually resembling those normally found in the small intestine. On the basis of these results we conclude that intestinal metaplasia involves mucin- and peptide-producing cells of the stomach in a variable manner, with no correlation between the two.

Adult↗

A non-parametric grading system for intestinal metaplasia: correlations with gastric tissue enzymes.

A novel method for grading intestinal metaplasia, with general applicability, is described. Highly significant agreement was found by kappa analysis both for intra-observer (k = 0.90) and for inter-observer (k = 0.85) variation, confirming the reproducibility of the method. The ranks derived by this method were correlated with gastric tissue levels of the enzymes beta-glucuronidase, lactic dehydrogenase (LDH), and %m-LDH. A significant (P less than 0.05) positive correlation was found between intestinal metaplasia and %m-LDH, but there was no correlation between intestinal metaplasia and beta-glucuronidase or LDH.

Gastric Mucosa↗

Morphometric definition and grading of gastric intestinal metaplasia.

Type I and type III intestinal metaplasia in gastric mucosa have been examined using morphometric methods. Tissue (volume per cent gland, lumen, epithelium, goblet cell vacuoles) and nuclear parameters (area, with related standard deviation, and form factors) were used as indicators of gland crowding, nuclear-cytoplasmic ratio, nuclear atypia, and pleomorphism. In type III intestinal metaplasia, there is significantly (i) greater nuclear pleomorphism, (ii) a higher nuclear-cytoplasmic ratio, and (iii) smaller and less numerous goblet cell vacuoles in both the upper and the lower parts of the crypts. These two parameters have significantly higher values in the lower than in the upper part of individual crypts. No cell population with large pleomorphic nuclei characterized type III metaplasia, though there was more variation in nuclear size.

Adult↗

Squamous metaplasia of the endometrium associated with HPV 6 and 11.

Although uncommon in the endometrium, squamous metaplasia, dysplasia, and squamous carcinoma have been observed. Associated human papillomavirus (HPV) infection is also unusual, due at least in part to the fact that HPV requires specific characteristics of the target epithelium for infectivity. We report a case of extensive squamous metaplasia with focal low-grade squamous intraepithelial neoplasia of the endometrium coexistent with low-grade cervical intraepithelial neoplasia and an invasive squamous carcinoma of the vagina. In situ hybridization studies revealed HPV types 6 and 11 in both the cervical and endometrial lesions. This is the first report to date to demonstrate squamous epithelial metaplasia and dysplasia of the endometrium, associated with HPV DNA of viruses typically of low oncogenic potential.

Carcinoma, Squamous Cell↗

Bronchiolarized metaplasia and interstitial fibrosis in rat lungs chronically exposed to high ambient levels of ozone.

The cellular and tissue changes in the lungs of rats were studied using electron microscopy following 20 months exposure to a range of ozone levels from 0.12 to 1.0 ppm. Male and female Fischer 344 rats were exposed and morphometric methods were used to determine the volume, surface area, and cellular changes observed in bronchiole-alveolar duct regions following chronic ozone exposure. No major gender-related effects were observed in response to chronic inhalation of ozone nor were significant effects of ozone exposure found in either terminal bronchioles or the proximal alveolar regions in animals chronically exposed to 0.12 ppm ozone. The proximal alveolar regions of animals exposed for 20 months to 0.5 and 1.0 ppm ozone were significantly altered with exposure. The high-dose, long-term exposure to ozone resulted in a pronounced increase in volume of both the interstitium and epithelium in the proximal alveolar regions. The thickening of the epithelium was due to a change in tissue type from the normal squamous epithelium to a cuboidal epithelium similar, but not identical, to that found in terminal bronchioles. This bronchiolar epithelial metaplasia of proximal alveolar ducts, which was dose related, was composed of differentiated ciliated and Clara cells similar to those found in terminal bronchioles. In addition, unique cells which contained morphologic features of many different cell types were observed. These cells, which may represent stem cells or differentiated but transformed cells, were found associated with the bronchiolar metaplasia of alveolar ducts. In conjunction with the epithelial changes, cellular and matrix components in the interstitium were increased with chronic exposure to 0.5 and 1.0 ppm ozone. All matrix components were increased including collagen, elastin, and basement membrane, as well as other acellular spaces which did not contain identifiable structures. The total volume of interstitial fibroblasts was also increased in the high-dose exposure group. Alveolar macrophages were increased only in the 1.0 ppm exposed animals. The cell and tissue changes in the terminal bronchioles were less pronounced indicating a relative resistance of this tissue to ozone and mainly consisted of a change in cell type from ciliated to Clara cells in the 1.0 ppm exposed animals. The relative resistance of bronchiolar tissue to high concentration ozone exposure and the extensive bronchiolar epithelial metaplasia may be an adaptive mechanism following chronic ozone exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Endotoxin potentiates ozone-induced mucous cell metaplasia in rat nasal epithelium.

People are exposed to a combination of environmental pollutants throughout their lives. Repeated exposures of one common pollutant, ozone, have been reported to cause the development of mucous cell metaplasia in the nasal transitional epithelium (NTE) of rats. The present study was designed to test the hypothesis that exposure to bacterial endotoxin, another toxicant ubiquitous to the environment, potentiates this metaplastic response in rat NTE. Rats were exposed to 0 or 0.5 ppm ozone 8 h/day for 3 days. After ozone exposure, rats were intranasally instilled with saline containing 0 or 100 micrograms endotoxin once daily for 2 days. Rats were killed 6 h or 3 days after the last intranasal instillation. Nasal tissue was processed for light microscopy and image analysis, or for isolation of total RNA. Mucous cell metaplasia was not detected in air/endotoxin-exposed rats, was observed in ozone/saline-exposed rats, and was most severe in ozone/endotoxin-exposed rats. At 6 h after instillation, amounts of intraepithelial mucosubstances (IM) were 4-fold greater in NTE of ozone/endotoxin-exposed rats as compared to controls. These IM levels were similar to those of ozone/saline-exposed rats. Mucin-specific mRNA (rMuc-5AC) levels were elevated in all treatment groups at this timepoint. At 3 days after instillation, amounts of IM in ozone/endotoxin-exposed rats were 10-fold greater than in controls and 5-fold greater than in ozone/saline-exposed rats. rMuc-5AC mRNA levels remained elevated in the ozone/endotoxin-exposed rats. Despite the fact that bacterial endotoxin alone does not cause a phenotypic change in rat NTE, it can augment the mucous cell metaplasia induced by a previous exposure to ozone.

Animals↗

Prepontine cyst lined by respiratory epithelium with squamous metaplasia: immunohistochemical and ultrastructural study.

An 8.5-year-old female presented with multiple episodes of aseptic meningitis and was found to have a cystic lesion in the prepontine region. Microscopic examination revealed a respiratory-type epithelium with squamous metaplasia. Like its normal analogue in the respiratory tract, the epithelium of these intracranial cysts can undergo squamous metaplasia when chronically irritated. The ultrastructural and immunohistochemical characteristics of the transition from ciliated epithelium to squamous metaplasia are described.

Brain Diseases↗

Alterations in sugar residues in squamous metaplasia in hamster tracheal explants induced by benzo(a)pyrene and its reversal by retinoic acid.

We have demonstrated that squamous metaplasia induced by benzo(a)pyrene (BP) in the hamster tracheal explants accompany distinct alterations in carbohydrate moieties in the epithelial mucosa. Most prominent alterations were the preferential binding of peanut agglutinin (PNA) and wheat germ agglutinin (WGA) in the basal cell layer in metaplastic lesions. In this study we examined if reversal of BP-induced lesions by all-trans retinoic acid (RA) results in the acquisition of normal carbohydrate composition by the tissue. Four lectins, PNA, WGA, Dolichos biflorus agglutinin, and Concanavalin A, in their horseradish peroxidase conjugates were used. In control explants the intercellular plasma membrane of basal and mucous cells exhibited no significant reaction with any of the lectins tested. In the metaplastic lesions induced by BP, PNA and WGA intensely stained the plasma membrane and intercellular spaces of basal and intermediate cell layers; the granular layer cells did not bind PNA whereas they were stained moderately with WGA. RA, which reversed the metaplasia, also conferred the tissue with lectin binding patterns similar to that of control explants. These results thus show that the reversal of metaplasia is accompanied by acquisition of the tissue's original carbohydrate composition.

Benzo(a)pyrene↗

Histogenesis and morphogenesis of epidermoid metaplasia in hamster tracheal organ explant culture.

The formation of epidermoid metaplasia was studied in hamster tracheal epithelium in long-term serum-free organ explant culture. Explants were cultured up to 5 weeks in CMRL 1066 with antibiotics and amphotericin B. At 3 weeks there were rare small foci of epidermoid metaplasia and they became larger and more numerous at 4 and 5 weeks. Three dimensional reconstructions from serial sections demonstrated that the small deep-seated foci were discrete and did not reach the epithelial surface, whereas the larger foci were expansive and involved the full thickness of the explant epithelium. Each small focus consisted of a few swollen electron-lucent basal cells attached to the basal lamina, covered by a layer of flattened electron-dense secretory cells which formed a tight-fitting cap over the basal cells. The altered secretory cells displayed moderately well-developed rough endoplasmic reticulum and tonofilament bundles. During the early stages of formation the deep-seated metaplastic foci were completely covered by a layer of normal appearing cuboidal to low-columnar secretory and ciliated cells. Expansion of the metaplastic foci occurred by addition of flattened, electron-dense secretory cells to the cap so that multiple layers of altered secretory cells covered a core of basal cells, analogous to the structure of an onion. The secretory cells became cornified and with time the foci broke through the columnar mucociliary surface layer. In well-advanced foci, the uppermost cornified squames (metaplastic secretory cells) exfoliated into the tracheal lumen. The study emphasizes similarities and differences between the morphogenesis and histogenesis of epidermoid metaplasia in vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Migration and maturation of Langerhans cells in squamous metaplasia of the rat trachea induced by vitamin A deficiency.

The migration and maturation of Langerhans cells (LCs) in rat tracheal squamous metaplasia due to vitamin A deficiency were investigated immunohistochemically and electron microscopically. In the early stage of metaplasia, i.e. basal cell hyperplasia, no LCs with Birbeck granules (BGs) could be found, but there were desmosome-free cells which had the morphological characteristic of immature LCs. They were clearly different from inflammatory cells such as macrophages and lymphocytes, and were, therefore, considered to be precursors of LCs. In the stage of stratification, small numbers of Ia- and protein kinase C type II (PKCII)-positive cells were recognized. Ultrastructurally they were immature LCs with ovoid nuclei, many free ribosomes and few dendrites. The cytoplasm was dark and a few BGs and atypical granules (AGs) could be seen in the Golgi area. In the early stage of cornification, LCs with partially intended nuclei, prominent nucleoli and well-developed Golgi complexes were found. There were many BGs and AGs and structures transitional between them in the Golgi areas. In epithelium showing mature squamous metaplasia, many Ia- and PKCII-positive dendritic cells could be seen. Most of these were typical mature LCs with lobulated nuclei, clear cytoplasm and prominent dendritic processes. The number of BGs and AGs were fewer than in the LCs found in the early stage of cornification, and these granules were distributed throughout the cytoplasm. In the final stage, where the basal cells had differentiated into a flatter epithelium, few LCs could be seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Spindle cell metaplasia arising in thyroid adenoma: characterization of its pathology and differential diagnosis.

Spindle cell metaplasia in thyroid adenoma or carcinoma is rare and its pathological features are not well characterized. Distinction of this entity from medullary or anaplastic carcinoma has an important clinical implication. We encountered a case of thyroid follicular adenoma associated with spindle cell metaplasia. It showed "tumor in tumor appearance" and neoplastic spindle cells were positive for thyroglobulin, thyroid transcription factor-1, vimentin and focally chromogranin A and somatostatin (SS). MIB-1 index was <1%. Ultrastructure of the spindle cells was reminiscent of follicular cell origin. From the findings from our case, spindle cell metaplasia appears to be a benign clinical entity, suggestive of multidirectional differentiation of follicular cells.

Adenoma↗