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Stromal osseous metaplasia in carcinoma of the bladder.

Osseous metaplasia of the stroma of carcinomas of the bladder is a rare finding that must be distinguished from osteosarcoma and carcinosarcoma. We report a case of multifocal osseous metaplasia in a high grade urothelial carcinoma with extensive glandular differentiation, arising in the base of the bladder of an 84-year-old man. Reports of 11 other cases of stromal osseous metaplasia in primary bladder carcinomas and of 5 cases of stromal osseous metaplasia in metastases of bladder carcinoma are reviewed.

Aged↗

Mucinous and squamous metaplasia of the renal pelvis.

Mucinous and squamous cell metaplasia of the transitional cell epithelium occurs in response to chronic irritation and is predominantly found in the bladder. When the 2 forms of metaplasia occur simultaneously they usually are associated with malignancy. We report 2 cases of mucinous and squamous metaplasia of the epithelium of the renal pelvis that were not associated with malignancy. This is believed to be the fourth report of this divergent metaplasia. The mechanism for these changes is discussed.

Adult↗

Recurrent osseous metaplasia of the cervix after loop electrosurgical excision.

BACKGROUND: Osseous metaplasia of the uterus is a rare pathologic entity usually affecting the endometrial cavity without cervical extension. It has been reported after abortion, in cases of chronic endometritis, and as a result of metabolic disorders as hypervitaminosis D, hyperparathyroidism, hypercalcemia, and hyperphosphatemia. CASE: A woman developed osseous metaplasia of the cervix shortly after loop electrosurgical excision procedure (LEEP) for severe cervical dysplasia. Normal transvaginal ultrasonograms before the LEEP, and failure to detect osseous metaplasia after histologic review of the tissue obtained from that procedure indicate that the osseous metaplasia had been induced by the LEEP. The heterotopic bone formation rapidly recurred after initial removal. Her serum calcium, phosphorus, and vitamin D levels were normal. CONCLUSION: LEEP may result in healing with metaplastic bone formation.

Adult↗

Apocrine cystic metaplasia: subgross pathology and prevalence in cancer-associated versus random autopsy breasts.

Focal apocrine metaplasia was studied in 293 whole human breasts by a subgross sampling technique with histologic confirmation. There were 186 breasts obtained from random autopsies. Another 107 breasts were obtained that were cancer-associated; these breasts either contained an invasive cancer or were situated contralateral to a cancer-containing breast. The observations support a lobular origin for most if not all apocrine metaplasia and demonstrate some correlation between the presence of apocrine metaplasia and coincident invasive breast cancer on either the contralateral or ipsilateral side. When extensive, apocrine metaplasia appears to be a useful phenotypic marker for tissue at a modestly increased risk for breast cancer. There were no breast carcinomas of the apocrine type in this series, supporting the belief that apocrine metaplastic epithelium has little intrinsic malignant potential. Finally, the data support the hypothesis that most breast cysts arise from apocrine metaplastic lobules.

Apocrine Glands↗

Intestinal metaplasia with adherent Helicobacter pylori: a hybrid epithelium with both gastric and intestinal features.

Helicobacter pylori seem to avoid areas of intestinal metaplasia in the gastric mucosa, but attachment of these bacteria to epithelium with the appearance of incomplete intestinal metaplasia has been documented. To characterize the nature of the epithelium to which H pylori was attached, we carried out an immunohistochemical study using monoclonal antibodies against gastric surface mucous cell mucins (M1), blood group-related carbohydrates antigens (Le(a), sialyl Le(a), Le(b), type 1H, and type 2H) and sialyl Tn antigen. The results of this study suggest that these areas of H pylori attachment represent a hybrid epithelium whose cells share characteristics of both gastric surface mucous cells and intestinal metaplastic cells. Whether all areas of incomplete intestinal metaplasia represent an intermediate stage between the normal gastric epithelium and the fully developed complete type of metaplasia remains to be determined.

ABO Blood-Group System↗

Well-differentiated adenocarcinoma mimicking complete-type intestinal metaplasia in the stomach.

We describe extremely well-differentiated intestinal-type adenocarcinomas of the stomach which mimic complete-type intestinal metaplasia. It is often difficult to discriminate such neoplastic lesions from inflamed or regenerative changes of intestinal metaplasia histologically. The aim of this study was to elucidate the clinicopathologic features of this unique carcinoma. Eight cases of gastric carcinoma of this type that were invasive beyond the muscularis mucosae were selected for mucin histochemical and immunohistochemical analyses. The carcinomas showed the following features: (1) predominant cells that had differentiated to mature neoplastic cells, with features of small intestinal absorptive cells (complete-type intestinal metaplastic cells), which have sialomucin, MUC2-positive cells, and brush border features detected by CD10 (56C6) staining; (2) neoplastic tubules in the mucosa showing branching, tortuous, anastomosing, and plexiform structures, which were more pathognomonic than the cytological features; (3) lesions distributed predominantly in the middle third of the stomach and surrounded by the fundic mucosa; and (4) zonal distribution of Ki-67-positive proliferative cells like those of intestinal metaplasia in the lower third to half of the cancerous tubules in the mucosa. The lesions consisted mainly of illusory carcinoma; however, there were foci of pathognomonic elements in some areas of the tumors. Several biopsy samplings of the lesion would ensure the histopathologic diagnosis. This unique lesion forms a subgroup of intestinal-type carcinomas of the stomach and is suggested to have a close link with complete-type intestinal metaplasia, previously ignored as a precancerous lesion.

Adenocarcinoma↗

The induction of intestinal metaplasia in rats by pyloroplasty or pyloroplasty plus vagotomy.

The influence of increased gastric pH on induction of intestinal metaplasia in the stomach of male JCL/SD rats was examined following surgical procedures of pyloroplasty or pyloroplasty and vagotomy. Twelve months after pyloroplasty plus vagotomy serum gastric concentrations were significantly higher (group II) than in rats receiving only pyloroplasty (group I) or in sham operated animals (group III). Additionally, trehalase activity was also higher in group II than in groups I and III. The incidence of intestinal metaplasia was significantly higher in groups I and II compared with the sham operated control animals (group III). This study indicates that intestinal metaplasia could be induced by surgical procedures such as pyloroplasty with or without vagotomy. Furthermore, elevation of the pH on gastric mucosa by such procedures may play a significant role in the subsequent development of metaplasia in the stomach.

Animals↗

Immunohistochemical analysis of apocrine breast lesions. Consistent over-expression of androgen receptor accompanied by the loss of estrogen and progesterone receptors in apocrine metaplasia and apocrine carcinoma in situ.

Apocrine phenotype is observed in a spectrum of breast epithelial lesions spanning from benign metaplasias to apocrine carcinoma. Apocrine metaplasia is a common finding in fibrocystic change of the female breast. In situ and invasive apocrine carcinomas are rare variants of ductal carcinoma. All breast apocrine lesions were shown to be associated with increased androgen hormones metabolism. We have evaluated 10 cases of apocrine metaplasia, 3 cases of in situ apocrine carcinoma and 10 cases of invasive apocrine carcinomas using immunostaining method for steroid hormone receptors (estrogen, progesterone, androgen), p53, bcl-2 and BRST-2. Paraffin embedded tissue and avidin-biotin peroxidase complex system were used. Androgen receptor (AR) expression is consistently increased in all cases of apocrine metaplasia when compared with surrounding normal, non-apocrine breast epithelium. This androgen receptor over-expression is accompanied by the loss of immuno-detectable estrogen and progesterone receptor, and also the loss of bcl-2. An identical pattern of immuno-reactivity is seen in in situ apocrine carcinomas, but it is observed with less frequency in invasive apocrine carcinomas, which only infrequently express AR as the only steroid hormone receptor.

Adult↗

Colonic metaplasia in the ileal pouch is associated with inflammation and is not the result of long-term adaptation.

Ileal pouch-anal anastomosis (IPAA) is the preferred surgical therapy for chronic ulcerative colitis (CUC) and familial adenomatous polyposis (FAP). Previous studies have demonstrated morphologic changes in pouch mucosa such as villous atrophy and crypt hyperplasia. These changes have been labeled "colonic metaplasia." The aims of this study were to determine whether these changes represent "normal" long-term adaptation of the nondiseased pouch or instead are present only in the setting of inflammation. Twenty-four patients were identified, greater than 5 years status post-IPAA for CUC, who underwent pouchoscopy for surveillance and had no history of pouchitis. Thirty-one patients were identified greater than 5 years status post-IPAA for CUC, who had a history of pouchitis and had undergone pouchoscopy at least 5 years status post-IPAA. Eight patients status post-IPAA for FAP were also identified. Biopsy specimens were reevaluated by a single, blinded pathologist for degree of inflammation, the presence of villous atrophy and crypt hyperplasia, and evidence of dysplasia. Among the patients with CUC, the inflammation score was greater in the pouchitis group, 13.2 +/- 1.2, compared to the nonpouchitis group, 4.0 +/- 0.5 (P < 0.0001). Median colonic metaplasia score was greater in the pouchitis group (4 [range 2 to 6]) vs. 2 (9 [range 0 to 6]; P < 0.0001). The colonic metaplasia score correlated with the inflammation score (Spearman coefficient r = 0.83; P < 0.0001). In the eight patients with FAP, the inflammation score was 5.1 +/- 0.9 and the median colonic metaplasia score was 1 (range 0 to 4). There was no evidence of dysplasia in any of the biopsy specimens. Patients without a history of pouchitis or symptoms of pouchitis have only a minimal degree of villous atrophy and crypt hyperplasia. These morphologic changes in the ileal pouch are found primarily in the setting of inflammation, and likely represent a reparative response.

Adaptation, Physiological↗

Squamous metaplasia of sebaceous gland.

Squamous metaplasia in the skin has been reported in the eccrine ducts as eccrine squamous syringometaplasia (ESS). To our knowledge, squamous metaplasia of sebaceous gland (SMSG) has not been described in human skin. Twenty-two biopsy specimens from patients with pressure lesions after cardiac surgery with extracorporeal circulation were evaluated for the presence of SMSG. Squamous metaplasia of sebaceous gland was identified in five of the eight scalp biopsies and none of the buttock biopsies. The squamous metaplasia began in the germinative outer layer and advanced in a centripetal way. We believe that SMSG is an unspecific change of the sebaceous cells secondary to a chronic injury. Ischemia appears to play a mayor role, but other factors such as chronic trauma or toxicosis can not be ruled out.

Carcinoma, Squamous Cell↗

28 K in squamous metaplasia of the bladder in patients with spinal cord injury.

Antibody to 28 K was used to examine sections of bladder biopsies obtained by cystoscopy from 14 patients with spinal cord injury (SCI). Most of the biopsies were obtained from patients with indwelling catheters during the investigation for possible malignancy. Sections of bladder were stained by the streptavidin procedure. The 28 K in the normal transitional epithelium of the bladder was in the superficial cells (umbrella cells). All the biopsies from patients with indwelling urethral catheters showed areas of squamous metaplasia usually associated with evidence of chronic inflammation. Cystitis cystica glandularis was also seen in one patient. Staining was most marked in the areas of squamous metaplasia with intracellular granular staining. The basal layers were not well stained. With marked squamous metaplasia, there was a superficial hyperkeratotic layer that stained variably and often did not stain at all. Staining was less marked in areas of hyperplasia, regenerating urothelium, and cystitis cystica glandularis. These findings raise the possibility that the presence of 28 K glycoprotein in the tissues or released into the urine may be used as an indicator of squamous metaplasia and chronic inflammation of the bladder.

Adult↗

Endocervical tubal metaplasia and adenocarcinoma in situ: role of immunohistochemistry for carcinoembryonic antigen and vimentin in differential diagnosis.

Eighteen cases of endocervical tubal metaplasia (tubal metaplasia) and 16 cases of adenocarcinoma in situ were reacted immunohistochemically for carcinoembryonic antigen (CEA) and vimentin. Whereas CEA was more frequently positive in adenocarcinoma in situ cases (63%) than in tubal metaplasia cases (39%), vimentin was not expressed in adenocarcinoma but was positive in 78% of cases of tubal metaplasia.

Adenocarcinoma↗

Histogenesis of gastric foveolar metaplasia following duodenal ulcer: a definite reparative lineage of Brunner's gland.

AIMS: We aimed to clarify the histogenesis of gastric metaplasia in the duodenal mucosa, particularly in association with a reparative lineage of Brunner's glands. METHODS AND RESULTS: Using immunohistochemical methods with recently developed antimucin monoclonal antibodies (mAbs) that distinguish foveolar and deep mucins of the gastric type, as well as mAb MIB-1, the histogenesis of gastric metaplasia was investigated in the duodenal wall of 20 surgically resected specimens. In duodenal ulcers extending into Brunner's glands with destruction of the muscularis mucosae, proliferating cells positive for MIB-1 were scattered in Brunner's glands. Interestingly, a group of proliferating cells was often seen next to the ulcerated surface. These cells were also positive for M1 (gastric-foveolar type mucin) but negative for M2 (deep gastric and Brunner glands' mucin). In regenerating ducts through granulation tissue, the proliferating cell zone was elongated, above which foveolar-type cells positive for M1 but negative for M2 were detected, indicating that the G-zone is newly established in Brunner's glands at the floor of an ulcer to produce gastric-foveolar cells. Subsequently, an organoid growth of the normal stomach mucosa is completed in the duodenum. CONCLUSIONS: This study indicates a possible histogenetic pathway of gastric metaplasia in close association with a reparative lineage of Brunner's glands, suggesting that the occurrence of the gastric-foveolar type epi-thelium is not a simple expansion of Brunner's duct but a true metaplasia.

Antigens, Nuclear↗

Mucinous metaplasia of the penis.

AIMS: To determine the incidence of mucinous metaplasia occurring in the foreskin or glans penis and any associated clinical or histopathological features. METHODS AND RESULTS: Following the recognition of two index cases, 100 other foreskin specimens were retrieved from the histopathology archives at Southampton General Hospital. The haematoxylin and eosin-stained slides were examined by a single observer to detect the presence of mucin-producing cells in the surface epithelium. The absence of mucinous metaplasia in negative cases was confirmed with mucin histochemistry. In total, four cases of mucinous metaplasia were identified, three involving the foreskin and one involving the glans penis. The age range was 51-80 years. Three cases were associated with Zoon's balanitis and the fourth showed mild non-specific balanitis. All four cases showed positive staining with both diastase periodic acid-Schiff and alcian blue. No mucin-producing cells were identified in non-inflamed or minimally inflamed specimens. CONCLUSIONS: Mucinous metaplasia of the penis is an uncommon but under-recognized condition. It is seen in the elderly and appears to be a metaplastic change associated with severe chronic inflammation, and possibly more specifically with Zoon's balanitis. Our study identified a case affecting the glans penis, a site not previously recorded.

Humans↗

Spatial distribution and histogenesis of colorectal Paneth cell metaplasia in idiopathic inflammatory bowel disease.

BACKGROUND AND AIM: Colorectal Paneth cell metaplasia (PCM) is known to be a sign of idiopathic inflammatory bowel disease (IBD), although its distribution and histogenesis are not fully understood. Objectives of this research were to investigate the spatial distribution of PCM in IBD and other forms of colitis (non-IBD), and to find stimuli causing PCM. METHODS: We studied multiple biopsy specimens from 181 patients with ulcerative colitis (UC), 159 with Crohn's disease (CD), 448 with non-IBD, and 78 normal controls. Paneth cell metaplasia frequency, at each colorectal site, was evaluated to find possible differences among diseases, phases of activity, and extents of disease. RESULTS: In non-IBD and controls, PCM was rarely (0-1.9%) seen at distal sites, but frequently (up to 48.7%) found at the ascending colon and cecum (P < 0.001). Paneth cell metaplasia frequency was significantly higher in IBD than in non-IBD patients and controls at distal sites (P < 0.001), but did not differ significantly between UC and CD, or among active, resolving, and quiescent phases. In UC, proctitis and left-sided colitis rarely displayed PCM at unaffected sites. Multiple logistic regression analysis revealed that PCM was positively associated with crypt distortion and mononuclear cell infiltration (P < 0.005), but negatively or not significantly associated with crypt atrophy, mucin depletion, acute inflammation, or phase of activity. CONCLUSIONS: Paneth cell metaplasia is a non-specific phenomenon in the proximal colon, but distal PCM, which occurs exclusively in affected mucosa, is a useful marker indicating IBD, even in the inactive phase. Regression analysis suggests that repair and regeneration may be the most potent stimuli causing PCM.

Adult↗

Evaluation of mucinous metaplasia of the prostate gland by mucin histochemistry.

OBJECTIVE: To evaluate the presence of mucinous metaplasia in normal and benign hyperplastic prostates, using stains for neutral and acidic mucins. PATIENTS, MATERIALS AND METHODS: Normal prostate glands were removed during the post-mortem examination of 11 consecutive subjects (median age 45 years, range 17-79) who had died accidentally. Specimens were also obtained from 10 patients (median age 70.2, range 61-82) undergoing suprapubic prostatectomy for prostatic hyperplasia. The specimens were examined histologically; sections were stained using the periodic acid-Schiff (PAS) method for neutral mucins and the alcian blue (AB) method at pH 2.5 for acidic mucins. The positive sections were also immunostained for high molecular weight cytokeratin (KER), and prostate-specific antigen (PSA) using the strept-avidin-biotin (SAB) method. RESULTS: Mucinous metaplasia was found in six of the normal prostates and in three of the hyperplastic glands. Usually, the cells were tall columnar, containing both AB- and PAS-positive material. The cells were negative both for PSA and KER. Mucinous metaplasia affected all ages, including a 17-year-old, and mostly involved the inferior periurethral area. CONCLUSION: Benign mucinous metaplasia was more frequent than previously appreciated, involved all ages, was mainly periurethral and did not correlate with the usual distribution of adenocarcinoma of the prostate.

Adenocarcinoma, Mucinous↗

Atrophic gastritis and intestinal metaplasia in Japan: results of a large multicenter study.

BACKGROUND: This study evaluated the relationship between Helicobacter pylori infection, atrophic gastritis and intestinal metaplasia in Japan. MATERIALS AND METHODS: This was a multicenter study performed in 21 centers in Japan. A total of 2455 individuals were enrolled. H. pylori status was determined by validated ELISAs. Atrophic gastritis was diagnosed by histology, endoscopy with Congo Red dye scattering or the Kimura-Takemoto endoscopic classification. RESULTS: Atrophic gastritis increased from 9.4% in those less than 20 years of age to > 70% in those aged 60 or older and was strongly associated with H. pylori infection. The overall prevalence of atrophic gastritis in H. pylori infection was 82.9% (1272/1534) compared with 9.8% (90/921) among uninfected (OR = 44.8; 95% CI = 34.7-57.8). Intestinal metaplasia was present in 43.1% (542/1258) of H. pylori positive persons compared with 6.2% (51/823) among the uninfected (OR = 11.5; 95% CI = 8.5-15.5). Atrophic gastritis in H. pylori positive Japanese was very high in the younger generation (38.5% in those aged 20 or less and 58.5% in those 21-30). CONCLUSIONS: Atrophic gastritis and intestinal metaplasia were strongly associated with H. pylori and not with aging. The fall in prevalence of H. pylori in Japan has not been associated with a corresponding fall in the prevalence of atrophic gastritis among those with H. pylori infection. The high prevalence of the precursor lesion, atrophic gastritis with intestinal metaplasia, among those with H. pylori infection suggests that the risk of development of early gastric cancer will continue to remain high in Japan.

Adult↗

Helicobacter pylori infection, mucosal atrophy and intestinal metaplasia in Asian populations: a comparative study in age-, gender- and endoscopic diagnosis-matched subjects.

BACKGROUND: It is known that the incidence and mortality rate of gastric cancer is high among Japanese and Chinese populations, but extremely low in Thai and Vietnamese populations. The aim of this study was to investigate the prevalence of Helicobacter pylori infection and the differences in the glandular atrophy and intestinal metaplasia scores in stomach specimens of Asian adult subjects of different races. MATERIALS AND METHODS: Chinese, Thai, Vietnamese and Japanese patients were matched by age, gender and endoscopic diagnosis, in order to compare the differences in incidence of H. pylori-related peptic ulcer disease and the prevalence of H. pylori infection among four Asian populations (n = 700). Glandular atrophy scores and intestinal metaplasia scores were also compared among four Asian populations divided into H. pylori-positive cases (n = 120, 109, 145, 80, respectively) and H. pylori-negative cases (n = 55, 66, 30, 95, respectively). RESULTS: Among peptic ulcers, gastric ulcer was more frequently seen in Japanese subjects than in the other Asian populations examined. On the other hand, duodenal ulcer was more frequently seen in other Asian populations than in Japanese subjects. The prevalence of H. pylori infection was similar in the Japanese (Tokyo) and Chinese (Beijing and Fuzhou) populations. It was higher in Thai (Chiang Mai) subjects compared with Japanese subjects. On the other hand, Vietnamese (Ho Chi Minh) subjects had significantly lower rates of H. pylori infection than Japanese subjects. The glandular atrophy and intestinal metaplasia scores in the stomach were significantly higher in the H. pylori-positive Japanese subjects than in H. pylori-positive subjects belonging to other Asian populations, except for the higher glandular atrophy scores in Chinese rather than Japanese subjects. On the other hand, there were no significant differences in the glandular atrophy and intestinal metaplasia scores in the angulus of the stomach among H. pylori-negative subjects belonging to the different Asian populations examined. CONCLUSIONS: Gastric ulcer was more common among Japanese subjects, while duodenal ulcer was more common among the other Asian populations examined. Japanese subjects with H. pylori infection showed more severe atrophic and metaplastic gastritis compared with that in other Asian subjects with H. pylori infection. These results may be related to the higher incidence of gastric cancer noted in Japanese subjects and the lower incidence of the cancer seen in Thai and Vietnamese patients.

Adult↗