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Atypical oxyphilic metaplasia of the endocervical epithelium: a report of six cases.

We report six examples of a hitherto undescribed atypical metaplastic change of endocervical glandular epithelium that we have designated atypical oxyphilic metaplasia of the endocervical epithelium. The patients ranged in age from 41 to 62 (mean 47.8) years; one was postmenopausal. Gravidity ranged from one to five (mean 2.8) and parity from one to four (mean 2.7). At the time of diagnosis one patient was taking combined oral contraceptives and one was taking tamoxifen for breast cancer. All of the lesions were incidental findings and were unassociated with a gross abnormality. Microscopically, affected endocervical glands were lined by large cuboidal or polygonal epithelial cells with dense, eosinophilic, focally vacuolated cytoplasm and varying degrees of nuclear atypia. Nuclei were enlarged, hyperchromatic, and frequently multilobated or multinucleated. Rare apical snouts were present in two cases. Stratification and mitotic activity were absent. Rare, focal periodic acid-Schiff positivity with and without diastase predigestion was present in three of three cases. Mucin staining was negative in two of three cases and focally stained luminal secretions in one of three cases. Three of three cases were negative for GCDFP-15 and carcinoembryonic antigen. Meaningful follow-up in four patients ranged from 1 to 15 (mean 5.5) years and was uneventful in all of them. Atypical oxyphilic metaplasia of endocervical epithelium represents yet another benign endocervical glandular atypia that must be distinguished from more serious lesions.

Adult↗

Increased E-cadherin expression in ovarian surface epithelium: an early step in metaplasia and dysplasia?

Ovarian surface epithelium (OSE), the source of common epithelial carcinomas, is a simple mesothelium that during carcinogenesis acquires complex epithelial characteristics normally found in tubal, endometrial, and endocervical epithelia. These characteristics include the intercellular adhesive molecule E-cadherin. We examined cryostat sections of 12 normal ovaries by immunofluorescence and immunocytochemistry to determine whether E-cadherin is a component of normal OSE that is retained in ovarian cancers or whether it, like many other epithelial characteristics, is acquired in the course of metaplasia and neoplastic progression. E-cadherin expression by OSE varied with its location within the ovary and with cell shape. It was present inconsistently on the ovarian surface but was increased in surface invaginations and particularly in epithelial inclusion cysts. Independent of location, E-cadherin was most prominent in columnar, variable in cuboidal, and absent in flat OSE. This relationship to cell morphology accounts for the increased E-cadherin expression in inclusion cysts, which are sites of frequent metaplastic and dysplastic changes. These results suggest that the morphologic variation of OSE reflects differences in E-cadherin-mediated intercellular adhesion. Thus, the appearance of this adhesion molecule in columnar OSE may represent an early step in the increased commitment to epithelial phenotypes that accompanies metaplasia and neoplastic progression of OSE.

Adenocarcinoma↗

Computed tomography demonstration of lipomatous metaplasia of the left ventricle following myocardial infarction.

Replacement of myocardium by fat, particularly of the right ventricle, is often diagnosed as arrhythmogenic right ventricular dysplasia. At autopsy, however, 68% of scars associated with chronic ischemic heart disease have shown fatty metaplasia in the scar. Four patients with a past history of previous myocardial infarctions and computed tomography demonstration of fatty change in left ventricular regions of hypokinesis and infarction are presented. It is proposed that these findings represent ischemic fatty metaplasia, an alternative etiology of fatty tissue replacing myocardium.

Adipose Tissue↗

Endoscopic diagnosis of intestinal metaplasia in Canada and Japan.

We carried out comparative studies on chronic atrophic gastritis with accompanying intestinal metaplasia using the methylene blue dye spraying, endoscopic technique on 167 Japanese and 77 Canadian outpatients free of gross stomach disease. In both population samples (Kyoto, Japan and St. John's, Newfoundland) with increasing subject age, the fundic-pyloric (F-P) border shifted cephalad indicating atrophy of the fundic mucosal glands. Japanese subjects, however, showed greater variation in location of the F-P border. The reduction in fundic gland area with aging was followed by intestinal metaplasia, the incidence and severity of which was greater in Japanese than in Canadian outpatients. From these data we conclude that a difference in the gastric mucosa in these two countries may be related to the pathogenesis of gastric cancer.

Adult↗

Low prevalence of gastric metaplasia in the duodenal mucosa in Peru.

We compared the prevalence of gastric metaplasia of the duodenal mucosa (GM) and its characteristics in 204 Peruvian patients from a low socioeconomic level with the corresponding prevalence reported in dyspeptic patients from a developed country, the United Kingdom. Gastric metaplasia was significantly less prevalent in the Peruvian than in the United Kingdom series. However, when present, GM was not significantly different in extent or frequency of colonization by Helicobacter pylori or association with active duodenitis, despite a higher prevalence of H. pylori-associated gastritis. Hypochlorhydria was markedly more frequent in the Peruvian than in the United Kingdom series. The finding of a low prevalence of H. pylori-colonized GM in patients with previously reported low prevalence of duodenal ulcer gives further support to a pathogenic link between both conditions.

Adolescent↗

Enhanced expression of inducible nitric oxide synthase in chronic gastritis with intestinal metaplasia.

Nitric oxide produced by inducible nitric oxide synthase (iNOS) has been claimed to be involved in gastritis; however, its characteristics are largely unknown. We assessed (1) iNOS expression in the human gastric mucosa in chronic gastritis and (2) the cytokines associated with iNOS expression. Gastric biopsy specimens were obtained from patients with chronic gastritis. Total RNA was isolated and reverse transcription-polymerase chain reaction (PCR) was performed semiquantitatively using specific primer sets for iNOS, interleukin (IL)-1beta, IL-8, IL-6, interferon-y, tumor necrosis factor-alpha (TNF-alpha), TNF receptors, IL-6 receptors, and sucrase, respectively. Helicobacter pylori infection was examined by the PCR assay. Reverse transcription-PCR analysis showed that expression of iNOS was detected in 10 of 23 samples. Expression of iNOS mRNA was closely correlated with expression of TNF-alpha and was observed frequently in subjects with intestinal metaplasia. The Helicobacter pylori gene was detected by PCR assay in all iNOS-positive cases. These results indicate that iNOS is predominantly expressed in the gastric mucosa with intestinal metaplasia and H. pylori infection. TNF-alpha is thought to be an important cytokine associated with iNOS expression.

Adult↗

Patterns of epithelial metaplasia in malignant gliomas. II. Squamous differentiation of epithelial-like formations in gliosarcomas and glioblastomas.

Six cases are reported (four gliosarcomas and two glioblastomas) in which the epithelial-like areas of glial anaplasia showed focal squamous cell differentiation, characterized by the development of epithelial whorls, keratin pearls and immunopositivity for cytokeratin. The expression of glial fibrillary acidic protein and the development of squamous metaplasia usually were mutually exclusive. Autopsy findings in two patients and clinical work-up in five failed to disclose a primary extraneural malignancy. It is suggested that squamous differentiation may represent an extreme form of epithelial metaplasia in a malignant glioma. This possibility should be kept in mind in the diagnostic evaluation of such cases, especially in view of the current emphasis on the immunomorphologic demonstration of intermediate filament tumor markers.

Adult↗

Papillary metaplasia of the endometrium: clinical and histopathologic considerations.

The clinical presentation and histopathology of three cases of papillary metaplasia of the endometrium are reported. This lesion is usually found with unopposed estrogen stimulation. Two of these patients were perimenopausal, and one was postmenopausal. In two of these patients chronic endometritis was found. Papillary metaplasia of the endometrium is infrequently cited and must be recognized as a benign entity.

Adenocarcinoma↗

Is type III intestinal metaplasia an obligatory precancerous lesion in intestinal-type gastric carcinoma?

This retrospective study was performed to assess whether type III intestinal metaplasia is an obligatory precancerous lesion of intestinal-type gastric carcinoma and to determine its possible use as a marker of enhanced cancer risk. From 48 consecutive patients with gastric cancer who underwent a gastrectomy over a 3-year period (mean age 72.0 years; 29 M/19 F), at least two sections from antrum, corpus and tumour-surrounding mucosa were obtained for the examination of presence and subtypes of intestinal metaplasia (IM). It was found that 77.1% of the carcinomas were of the intestinal type and 22.9% of the diffuse type. The intestinal-type was more often found in males (P = 0.01); the mean age at diagnosis in this type was higher than in the diffuse cancer group (P = 0.004). There was a high prevalence of total IM in both the intestinal (75.7%) and diffuse group (88.9%). Type I IM was predominant in antrum and corpus of patients from both groups. Type III IM was only found among patients with intestinal-type carcinoma. However, its prevalence was rather low (26.3%). Therefore the absence of this lesion in patients with other risk factors cannot be used as an argument for lowering the degree of surveillance and its presence seems to be sufficient indication for long-term follow-up.

Aged↗

Association of spasmolytic polypeptide-expressing metaplasia with carcinogen administration and oxyntic atrophy in rats.

Spasmolytic polypeptide (TFF2)-expressing metaplasia (SPEM) is a gastric metaplastic lineage associated with the development of intestinal-type gastric adenocarcinoma. To study the etiology of this potential neoplastic precursor metaplasia, we used surgical rat models of remnant gastric adenocarcinoma studied with and without exposure to nitroso carcinogen. Animals with truncal vagotomy without duodenogastric reflux procedures demonstrated normal mucous neck cell spasmolytic polypeptide (SP) immunostaining. In these animals, anti-proliferating cell nuclear antigen (PCNA)-labeled nuclei were found in the normal midgland progenitor zone. Rats that received anatomic alterations that augmented the degree of duodenogastric reflux, however, revealed expansion of basally placed SP immunoreactive cells with early phenotypic changes of SPEM. Seventy percent of animals with antrectomy and carcinogen (with or without vagotomy) developed SPEM at the base of the gastric mucosa. In association with the appearance of this metaplastic lineage, a distinct second zone of PCNA-labeled nuclei developed in the deepest portion of the mucosa. Of interest, three animals demonstrating these changes developed intestinal-type gastric adenocarcinoma. Finally, we studied the immunostaining pattern of intrinsic factor, normally a chief cell marker in rat fundic mucosa. In animals with SPEM, we observed coexpression of SP and intrinsic factor in SPEM cells at the base of the mucosa. These findings support our hypothesis that SPEM develops from a second progenitor cell population, reflecting either the unmasking of a cryptic zone or transdifferentiation of chief cells.

Animals↗

Peribronchiolar metaplasia: a common histologic lesion in diffuse lung disease and a rare cause of interstitial lung disease: clinicopathologic features of 15 cases.

Peribronchiolar metaplasia (PBM) is a histologic lesion consisting of peribronchiolar metaplasia (PBM) of bronchiolar-type epithelium. Although widely recognized, PBM has received little attention in the pathologic literature and is not known to have clinical significance. We identified 15 cases in which PBM was the only major histologic finding in surgical lung biopsies from patients with interstitial lung disease (PBM-ILD), and we reviewed the clinical, imaging, and pathologic findings. The mean age was 57 years (range, 44-74 years) with 13 females and 2 males. One patient had been a welder with fume and asbestos exposure; another had pigeon exposure. Smoking history was available for 13 patients: three current smokers, one cocaine user, two former smokers, and seven never smokers. Three patients had collagen vascular disease. One had elevated serum antinuclear antibody titers. Pulmonary function data were available for 10 patients: one obstructive, five restrictive, two mixed obstructive and restrictive, and two normal. Computerized tomography in 7 patients showed mosaic attenuation in 3 patients and air trapping in 1 patient; no bronchiectasis, septal lines, or honeycombing were seen in any cases. All 11 patients with available follow-up are alive; 4 of them have experienced symptomatic improvement (follow-up, 0.6-6.9 years; mean, 2.4 years). PBM was found focally in other interstitial lung diseases, which were assessed for this lesion: 59% of usual interstitial pneumonia (17 of 29), 50% of nonspecific interstitial pneumonia (10 of 20), desquamative interstitial pneumonia (3 of 6), hypersensitivity pneumonitis (9 of 18), and 11% of respiratory bronchiolitis (2 of 18). In summary, PBM is a common histologic finding in various interstitial lung disorders. It is rarely the sole major lung biopsy finding in patients presenting with interstitial lung disease (PBM-ILD). Patients are mostly older women, with mild symptoms and CT findings. Survival appears to be favorable.

Adult↗

Distinct molecular alterations in complex endometrial hyperplasia (CEH) with and without immature squamous metaplasia (squamous morules).

Several molecular alterations, most commonly PTEN mutations but also K-ras mutations, microsatellite instability, and beta-catenin mutations have been detected in endometrioid endometrial carcinoma (EEC). Specifically, mutations in the beta-catenin gene are seen in 15% to 20% of EECs, whereas immunohistochemical expression of beta-catenin ranges from 13% to 44%, nuclear staining being concentrated in areas of immature squamous metaplasia (squamous morules). Complex endometrial hyperplasia with atypia (CEH-A) is a well-known precursor of EEC, which can also show immature squamous metaplasia. In this study, we compared the immunohistochemical and molecular profiles of 13 CEH-A with and 11 CEH-A without squamous morules (SM) for mutations of beta-catenin, PTEN, K-ras, and microsatellite instability (MSI). In all cases of CEH-A with SM, beta-catenin immunostaining showed strong and diffuse nuclear expression in areas of SM and weak to moderate nuclear expression in the glandular component. Six different beta-catenin mutations were found in 7 of 13 cases (54%) (G34E, G34V, S33C, D32Y, S33F, D32A); however, no mutations of the PTEN or K-ras genes were identified. beta-Catenin immunostaining showed focal nuclear staining in only 2 cases of CEH-A without SM. Only 1 case had a beta-catenin mutation (S45A), which was associated with a K-ras mutation (G12D). Another 3 cases had both PTEN and K-ras mutations (C296Stop Ex 8 and G12V, 244del C Ex 7 and G12D, 251ins TGAT Ex 7 and G13D), and one had a PTEN mutation (G230E Ex 7) only. Of all 24 cases, only 1 case of CEH-A without SM showed MSI. In conclusion, marked differences in the molecular profiles regarding beta-catenin, PTEN, and K-ras mutations were observed between CEH-A with and without SM. beta-catenin mutations might represent a signaling pathway leading to a distinctive morphology in hyperplastic/neoplastic endometrium with SM. Other molecular events such as K-ras or PTEN mutations are likely to occur in CEH-A independently from beta-catenin. Furthermore, morphologic differences between CEH-A with SM and CEH-A without SM seem to correlate, at least to some extent, with the clinical course of the disease. In our series, cases of CEH-A with SM and beta-catenin alterations appeared to have a less aggressive behavior when compared with CEH-A without SM and with K-ras and PTEN mutations.

Adult↗

Gastric foveolar metaplasia with dysplastic changes in Brunner gland hyperplasia: possible precursor lesions for Brunner gland adenocarcinoma.

Cases of adenocarcinomas developed in Brunner gland hyperplasia (BGH) have been sporadically reported. Herein, we report the morphologic spectrum of hyperplastic changes culminating into dysplasia and carcinoma in 722 cases of BGH listed in our files. Fifteen of these cases showed dysplastic changes, with 8 graded as low-grade dysplasia, 5 as high-grade dysplasia, 11 as atypical hyperplasia, and 2 as invasive carcinoma, although each frequently coexisted in the same tumor. In two carcinomas, one had high-grade dysplasia in the mucosa, and another had only atypical hyperplasia. Interestingly, hyperplastic glands around dysplastic foci were associated with gastric foveolar metaplasia and papillary configuration in 13 cases, 11 of which showed a gradual increase in nuclear atypism in the transition from metaplastic to dysplastic glands. All of the metaplastic gastric glands showed diffuse and strong immunopositivity for gastric foveolar mucin (MUC5AC). Immunohistochemical profiles also supported the concept of a continuous spectrum in carcinogenesis from gastric foveolar hyperplasia through atypical hyperplasia or dysplasia and eventually to frank adenocarcinoma. The results of our study suggest, therefore, that dysplastic and/or carcinomatous change does occur in BGH, that they form the continuous morphologic spectrum, and that papillary foveolar metaplasia may be a precursor lesion in the process of carcinogenesis with a background of BGH.

Adenocarcinoma↗

p16INK4A immunohistochemistry is superior to HPV in situ hybridization for the detection of high-risk HPV in atypical squamous metaplasia.

In situ hybridization (ISH) assays for high-risk human papillomavirus (HR-HPV) and immunohistochemical (IHC) assays for surrogate markers such as p16 can be useful in detecting HR-HPV in cervical dysplasia, but the use of these markers in problematic cervical biopsies has not been well-established. We evaluated 3 chromogenic ISH assays (Ventana INFORM HPVII and HPVIII and DakoCytomation GenPoint) in conjunction with p16 IHC and HPV polymerase chain reaction in a study set consisting of 12 low-grade squamous intraepithelial lesions, 16 high-grade squamous intraepithelial lesions, and 30 benign cervix samples. A test set of 28 cases of atypical squamous metaplasia were also evaluated withVentana HPVIII ISH and p16 IHC. In the study set, the sensitivity of the DakoCytomation ISH assay (which detects HPV subtypes 16, 18, 31, 33, 35, 39, 45, 52, 56, 58, 59, and 68) was similar to the Ventana HPVII assay but less than that of the Ventana HPVIII ISH assay (both of which detect HPV subtypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 66) and less than p16 IHC (55.6% vs. 53.6 vs. 69.2% vs. 82.1%). All HPV ISH assays exhibited 100% specificity. p16 reactivity consisted of 2 patterns: focal strong and diffuse strong. Because focal strong p16 reactivity was identified in benign squamous epithelium (6.7% cases) and dysplastic epithelium, it was considered an equivocal result and only diffuse strong reactivity was considered to be specific for the presence of HR-HPV. In the squamous intraepithelial lesions study set, the difference in sensitivity between Ventana HPVIII ISH and p16 was not statistically significant. However, in the atypical squamous metaplasia test set cases, p16 reactivity (focal strong and diffuse strong) was significantly more sensitive than Ventana HPVIII ISH in correlating with the presence of human papillomavirus as detected by polymerase chain reaction (83.3% vs. 33.3% P=0.004). Because focal strong p16 reactivity is less specific, cases with this staining pattern are considered atypical and require further evaluation by other means. Overall, p16 IHC is considered the best candidate for the initial assessment of cervical biopsies that are histologically indeterminate for dysplasia given its wide availability, comparative ease of interpretation, and high sensitivity and specificity.

Adolescent↗

Osseous metaplasia in the setting of nephrogenic fibrosing dermopathy.

BACKGROUND: Nephrogenic fibrosing dermopathy (NFD) is a new skin-fibrosing disorder associated with renal dysfunction. It is marked by the acute onset of induration involving the upper and lower limbs, and it is characterized by distinctive histopathologic findings. METHODS: We report the case of a patient on hemodialysis who presented initially with the characteristic clinical and pathological features of NFD. The patient progressively developed painful hyperkeratotic spicules on both thighs and bone metaplasia was confirmed. RESULTS: Histological studies were performed at different stages of the disease showing an evolution from the well-known initial phase of NFD, characterized by thickening of the dermis, increased number of fibroblast-like cells, and mucin deposits, to an end stage characterized by the presence of dermal ossification. CONCLUSIONS: We report the exceptional finding of bone metaplasia in the setting of a case of NFD.

Adult↗

Quantitation of gastric intestinal metaplasia by morphometry in Japanese patients.

With the aid of an image processor, the length of the intestinal metaplasia (IM) was recorded in 33 gastrectomy specimens (23 with early gastric cancer and 10 with gastric peptic ulcer). A total of 1917 sections were analyzed. The length of the areas with IM and the total length of the muscularis mucosa were measured in individual sections. The resulting ratio (length of IM/length of muscularis mucosa) was noted as the intestinal metaplasia index (IMI), as an expression of the extension of IM in the specimens. The IMI was influenced by the age of the patient and by the histologic type of the tumor: a higher IMI was found among older patients and among patients with adenocarcinoma of intestinal type. A comparison with a similar study done in gastrectomy specimens from Swedish patients indicates that despite the latter group being older, and the tumors being more advanced, the IM was much more extended in the gastric mucosa of the Japanese patients with gastric adenocarcinomas of intestinal type. From the results it is suggested that extended IM in the gastric mucosa may have some bearing on the histogenesis of gastric carcinomas, particularly adenocarcinomas of intestinal type.

Adenocarcinoma↗

Review article: prevalence of Barrett's oesophagus and metaplasia at the gastro-oesophageal junction.

Barrett's oesophagus, a complication of chronic gastro-oesophageal reflux disease, is the premalignant lesion for oesophageal and gastro-oesophageal junction adenocarcinoma. Described in the 1950s by Norman Barrett, the diagnostic criterion for this lesion has evolved significantly over the last three decades. Endoscopic Barrett's oesophagus requires the recognition of columnar mucosa in the distal oesophagus; documentation of metaplastic tissue is confirmed by random biopsies. Given this changing definition of Barrett's metaplasia, the prevalence rates vary in the literature depending on the diagnostic criteria applied. However, it is generally accepted that approximately 10% of patients with chronic gastro-oesophageal reflux disease will be diagnosed with this condition. There are no population-based studies on the prevalence of Barrett's oesophagus, but emerging data indicate that it may be equally prevalent in asymptomatic individuals. These studies require confirmation. Although the incidence of oesophageal adenocarcinoma is increasing rapidly, it is unclear whether the true incidence of Barrett's oesophagus is increasing at the same time. On the other hand, metaplasia at the gastro-oesophageal junction appears to be distinct from Barrett's oesophagus, is probably not related to chronic gastro-oesophageal reflux disease and is a common finding if routine biopsies are obtained at the gastro-oesophageal junction. This article reviews our current understanding of the diagnosis, definition and prevalence of both of these lesions.

Barrett Esophagus↗

Cytological changes associated with tubo-endometrioid metaplasia of the uterine cervix.

Two women who had undergone previous cervical surgery for the treatment of glandular intraepithelial neoplasia (GIN) and cervical intraepithelial neoplasia (CIN), were found to have severely dyskaryotic cells of glandular and metaplastic type in follow-up cervical smears. A third patient was found to have similar abnormal cells in a routine screening smear. All of the patients were subjected to either hysterectomy or cervical conization and in all cases histological examination showed tubo-endometrioid glands in the endocervix, well away from the uterine isthmus, with no associated endometrial stromal tissue. All of the cervical smears were reviewed and cytological features that facilitate the distinction between tubo-endometrioid metaplasia and squamous or glandular dyskaryosis were identified. These features include the smaller size of affected cells, more marked nuclear hyperchromasia, inconspicuous nucleoli, the formation of glandular structures, the lack of discrete squamous dyskaryosis and the absence of the typical 'feathering' noted with GIN. The possibility of tubo-endometrioid metaplasia should be considered when atypical glandular or metaplastic cells are noted in cervical smears, particularly, but not exclusively, in women who have been treated for CIN or GIN. In the presence of these changes clinicians should rebiopsy the cervix before embarking on further unnecessary surgery which may adversely affect fertility and pregnancy, particularly in younger patients.

Adult↗