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PubMed1991

Clustering of colorectal neoplasia: characteristics of coexisting adenomas in patients with severely dysplastic polyps or invasive (malignant) polyps as compared to patients with benign adenomas or carcinomas.

This study compared the size, histology and morphology of coexisting neoplastic polyps found in colonoscopy, and evaluated the clustering of these polyps in patients with either colorectal carcinoma, cancerous polyps or benign adenomas. Patients were divided by their most malignant form of neoplasia: Group A included 58 patients with early invasive cancerous polyps, and Group B included 73 patients with in situ carcinoma within an adenoma. Group C consisted of 335 patients with benign adenomas, and Group D had 289 patients with colorectal carcinoma. There were no significant differences between the four groups regarding sex, age and ethnicity. The cancerous polyps were significantly larger than the benign polyps. There were significantly (P less than 0.01) more patients with multiple (greater than or equal to 5) colonic lesions in Groups A or B than in Groups C or D. Coexisting polyps were much closer to the index growth, and demonstrated more severe dysplastic changes in the case of cancerous polyps than those associated with benign polyps or cancer. Based on our data we speculate that cancerous polyps are not merely a middle link in adenoma-carcinoma sequence, but rather mark a subset of patients who are especially prone to develop neoplastic changes in their colonic mucosa. These patients should be included in a more strict colonoscopic surveillance programme.

Adenocarcinoma↗
PubMed1998

Simian virus 40 T antigen-induced gonadotroph adenomas: a model of human null cell adenomas.

The cell of origin of human null cell pituitary adenomas is disputed. Although these tumors, by definition, do not produce any of the anterior pituitary hormones in vivo, they have been shown to express gonadotropin subunit genes, release gonadotropin hormones in vitro, and express the gonadotroph-associated transcription factor steroidogenic factor-1. However, they demonstrate variable responses to releasing hormones in vitro, raising questions about their origin from differentiated gonadotrophs or pluripotent stem cells. In this set of experiments, transgenic mice carrying a temperature-sensitive mutant (TSA58) of simian virus 40 T antigen driven by human FSHbeta regulatory elements were produced. These animals developed slow growing, multifocal pituitary nodules that demonstrated secretion of FSH with serum FSH levels 10-fold higher in male transgenic animals and 5-fold higher in female transgenic animals than those in nontransgenic controls. Anterior pituitary pathology progressed from diffuse gonadotroph hyperplasia to nodular adenomas with persistent, but decreasing, immunoreactivity for FSHbeta and LHbeta. Ultrastructural characteristics of the tumors were identical to those of human null cell adenomas. These results support the hypothesis that human null cell adenomas are derived from gonadotrophs and provide an animal model for further study of this disease.

Adenoma↗
PubMed1993

Basic fibroblastic growth factor stimulates prolactin secretion from human anterior pituitary adenomas without affecting adenoma cell proliferation.

The effects of human recombinant basic fibroblastic growth factor (bFGF) on the secretion and/or proliferation of 26 human anterior pituitary adenomas secreting PRL alone (6 tumors), PRL and GH (18 tumors), or GH alone (2 tumors) were examined. Secretory studies were performed over 4 h, 4 days, and 21 days, and proliferation studies over 4 days. The acute effect of bFGF on secretion over 4 h was examined in 10 tumors. bFGF (10 nmol/L) increased PRL compared to that in controls (100%) in 2 tumors (126% and 290%; P < 0.05) and PRL and GH in a third tumor (183% and 133%, respectively; P < 0.05), whereas 7 tumors remained unaffected. Fourteen tumors were studied over 4 days. bFGF (10 nmol/L) increased PRL secretion in 9 of 11 tumors (117-525%; P < 0.05) cosecreting PRL and GH and in all 3 tumors secreting PRL alone (156%, 183%, and 691%; P < 0.01). Dose-response curves with 0.1, 1, and 10 nmol/L bFGF in 2 of these tumors cosecreting GH and PRL showed that stimulation was achieved with all 3 concentrations. bFGF (10 nmol/L) stimulated GH secretion in 2 of 11 mixed tumors (159% and 196%, respectively; P < 0.05). In 2 tumors studied over 3 weeks, 5 nmol/L bFGF stimulated PRL secretion progressively without affecting GH secretion (106% and 207%; P < 0.05). Tissue proliferation was determined by double immunostaining after bromodeoxyuridine incorporation for 1 h in 7 tumors after 4 days. The labeling index did not exceed 1.2% in any tumor, and there was no effect of 10 nmol/L bFGF on the proliferation of adenoma cells. These results suggest that bFGF may have a paracrine role in the stimulatory regulation of PRL secretion in human pituitary adenomas, and these effects are most likely due to increased hormonal synthesis. An in vitro cell culture system can be used to study proliferative potential. However, bFGF is not mitogenic for human anterior pituitary adenomas secreting PRL and PRL plus GH in vitro.

Adenoma↗
PubMed1985

[The effects of metoclopramide and dopamine on aldosterone secretion in cultured adrenocortical adenoma cells and adjacent non-adenoma cells from patients with primary aldosteronism].

Several authors have reported that metoclopramide (MCP), a dopaminergic antagonist, stimulates aldosterone secretion and that dopamine (DA) inhibits the MCP-mediated aldosterone secretion in man. However, many controversial results have been reported relating to the direct effect of MCP and DA on the secretion of aldosterone by adrenocortical cells in in vitro experiments. The present studies were designed to determine whether or not MCP and DA exerts its effect directly on the cultured human adrenocortical adenoma cells and adjacent non-adenoma cells obtained from patients with primary aldosteronism. A bolus intravenous injection of 10 mg MCP significantly increased the plasma aldosterone concentration (PAC) from 255 +/- 57 pg/ml (mean +/- SD) to 386 +/- 98 pg/ml after 15 min in patients with primary aldosteronism. But MCP (10(10)-10(-6) M) failed to increase aldosterone secretion from both adenoma cells and non-adenoma cells in culture. DA (10(-9) and 10(-6) M) did not suppress the basal secretion and the enhanced secretion of aldosterone by A II or ACTH in cells of either culture. The analysis by HPLC showed that 57% of dopamine hydrochloride added in the medium was preserved after 60 min incubation. These results suggest that MCP and DA do not act directly on the human adrenal glomerulosa cells in the regulation of aldosterone secretion.

Adenoma↗
PubMed1993

Detection of growth hormone, prolactin and human beta-chorionic gonadotropin mRNA in growth hormone-secreting pituitary adenomas and in prolactin-secreting pituitary adenomas by in situ hybridization using a non-isotopic detection method.

A non-isotopic in situ hybridization method with digoxigenin-labelled probes was used to examine growth hormone (GH), prolactin (PRL) and human beta-chorionic gonadotropin (beta-hCG(LH)) gene expression in 63 pituitary tumours in acromegaly and 20 adenomas in hyperprolactinaemia. hCG and LH were detected simultaneously because of the extensive homology (more than 90%) of their mRNA sequences (1). A comparison with former results obtained with 35S-labelled probes shows the value of the easier and faster non-isotopic method. Additionally, immunohistochemical data are included to give even more evidence for the synthesis of the respective hormones by the tumour cells. In all 63 adenomas in acromegaly, GH mRNA was revealed in 59 PRL mRNA and in 36 beta-hCG(LH) mRNA. A positive immunostaining for GH was found in all, for PRL in 40, and for beta-hCG(LH) in 34 adenomas. The comparison of the two in situ hybridization methods revealed no differences concerning GH mRNA detection, but not all tumours positive after non-isotopic PRL and beta-hCG(LH) mRNA detection showed signals with the radioactive method. Referring to the 20 PRL-secreting adenomas, PRL gene expression was demonstrable in all, GH mRNA in 12, and beta-hCG(LH) mRNA in 2 cases. Comparing the positive results of immunohistochemistry with those of in situ hybridization, correspondence was found in 19 cases for PRL, in 5 cases for GH and in no case for beta-hCG(LH).

Acromegaly↗
PubMed1983

Follow-up after colorectal polypectomy. II. Repeated examinations of the colon every 6 months after removal of sessile adenomas and adenomas with the highest degrees of dysplasia.

Fifty-five patients with colorectal sessile adenomas and adenomas with the severest dysplasia were followed up every 6 months with colonoscopy and/or double-contrast enema during 4 years, after a clean colon had been obtained, by repeated colonoscopy within 3 months after piecemeal polypectomy. The repetition at 3 months resulted in detection of two cancers. An overlooked cancer was detected at 1 year, and another cancer was diagnosed between examinations. Risk of new adenomas (19 patients) was related to original size, number, and glandular structure of the polyps. Twelve of the 19 patients had new polyps above the rectum. The 336 colonoscopies were complicated by 3 laparotomies, made necessary by perforation and bleeding. The results suggest that intervals between examinations of patients with the present type of adenomas may be prolonged, and patients are now allocated at random to colorectal follow-up examination every 6 and 12 months.

Adenoma↗
PubMed2001

[Silent adenoma type 3: the importance of the ultrastructural study in the differential diagnosis of pituitary adenoma associated with hyperprolactinemia in a case].

The association of hyperprolactinemia over 100 ng/ml and a pituitary adenoma is usually diagnostic of prolactinoma. However type 3 pituitary adenomas can occur with similar serum prolactin values. We report a 31 years old woman that consulted due to headache and photopsiae. She had a serum prolactin level of 148 ng/ml and imaging studies showed a solid tumor that occupied the sellar region and most of the left temporal fossa. The tumor was partially resected and the patient recovered her lost visual field. Light microscopy showed an acidophilic and in part chromophobe adenoma. Immuno-histochemistry was positive for prolactin and growth hormone. Electron microscopy disclosed features of a silent type 3 adenoma such as big cells with cytoplasmic prolongations, pleomorphic nuclei and a greatly developed rough endoplasmic reticulum.

Adenoma↗
PubMed1986

Presence of neurophysins in the human pituitary corticotrophs, Cushing's adenomas, and growth hormone-producing adenomas detected by immunohistochemical study.

Neurophysins have been recognized as the carrier proteins of vasopressin and oxytocin. The distribution of neurophysins is immunohistochemically confirmed in the hypothalamus, median eminence, and posterior lobe of the pituitary gland. The authors detected neurophysins in the human corticotrophs and pituitary adenomas with the use of the immunohistochemical method with antiserum to human neurophysins, which did not cross-react with adrenocorticotropic hormone (ACTH), beta-endorphin, and corticotropin-releasing factor. All of ten pituitary glands obtained by autopsy revealed the presence of neurophysin-positive cells in the anterior, intermediate, and the posterior lobes. The neurophysin-positive cells were similar to the corticotrophs in shape and distribution. Simultaneous staining for ACTH and neurophysins in the serial sections revealed that neurophysin-positive cells were also ACTH-positive. One hundred twenty-four cases of pituitary adenoma operated upon were investigated. All of 7 Cushing's adenomas were composed of neurophysin-positive cells. Six tumors with giantism showed sparsely distributed neurophysin-positive cells. No neurophysin-positive cells were observed in any other cases. This study is the first reported evidence of the presence of neurophysins in the human corticotrophs and pituitary adenomas.

Adenoma↗
PubMed1982

Liver adenoma with granulomas. The appearance of granulomas in oral contraceptive-related hepatocellular adenoma and in the surrounding nontumorous liver.

A 31-year-old woman who had taken oral contraceptives regularly for seven years was found to have a hepatocellular adenoma in the left lobe of her liver. An unusual microscopic feature of the resected specimen was the presence of numerous noncaseating, epithelioid granulomas in both the adenoma and the surrounding nontumorous liver. The literature contains brief mentions of granulomas occurring within an occasional hepatocellular adenoma, but a search uncovered no reports of granulomas occurring in both the tumor and the surrounding nontumorous liver. This further evidence of the occurrence of epithelioid granulomas with hepatocellular adenomas suggests a possible relationship between tumor antigens and the granulomatous response.

Adenoma↗
PubMed1986

Endoscopic criteria for malignancy in colon adenomas. The dunce cap adenoma.

Histologic criteria for malignancy in colonic adenomas have been well established, but little has been written regarding the gross or macroscopic appearance of malignant adenomas. The following nine criteria, listed in order of most to least importance, were used to endoscopically evaluate polypoid lesions of the colon: friability, ulceration, firmness, the dunce cap sign, lobulation, asymmetry, size, macroscopic growth pattern, and color. Three cases of the dunce cap adenoma are reported in detail. In evaluating 121 consecutive colonic lesions, 87 percent were resected endoscopically. Eleven carcinomas, three villous adenomas, and two lipomas were not removed via the endoscope.

Adenocarcinoma↗
PubMed1999

Helicobacter pylori and the risk of colonic adenomas. Colorectal Adenoma Study Group.

AIMS: Previous studies have found a positive association between Helicobacter pylori infection and colorectal adenomas. The aim of the present study was to examine this association while taking possible confounding factors into account. METHODS: 98 serum samples were available from 182 patients with colorectal adenomas who entered a case-control study of colorectal adenomas and diet. The H. pylori status in patients was compared with a hospital control group and a population control group. RESULTS: H. pylori IgG antibodies were more common in colorectal polyp patients compared with either control group, the prevalence being 79% in cases compared with 62% in both control groups. The corresponding RR was 1.4 (0.76-2.6) compared with hospital controls and 2.1 (1.1-3.9) compared with population controls. After adjusting for possible confounding variables the association between H. pylori status and adenoma risk was even more marked. There was an RR of 1.6 (0.80-3.4) compared with hospital controls and an RR of 2.6 (1.3-5.4) compared with population controls, the latter association being statistically significant. CONCLUSION: These findings suggest a statistically significant association between H. pylori infection and colorectal polyps. A possible mechanism might be increased gastrin levels in H. pylori-infected subjects which exhibit a trophic effect on colonic mucosa.

Adenomatous Polyposis Coli↗
PubMed1994

p53 Protein accumulates in Cushings adenomas and invasive non-functional adenomas.

The p53 protein, a negative regulator of cell growth, plays an important role in the pathogenesis of many human tumours following gene mutation and/or deletion. We screened a large number of sporadic pituitary tumours for p53 protein accumulation suggestive of gene mutation. Samples were divided into benign adenomas (n = 95) and invasive tumours with local or distant invasion (n = 26). All main tumour classes were represented. Putative p53 mutations were detected by immunohistochemistry on paraffin-embedded sections using polyclonal CM-1 and monoclonal DO-7 and PAb1801 antibodies. Results were compared to normal post-mortem pituitary tissue controls (n = 17). p53 protein accumulation was detected in invasive tumours (16%), but only in corticotrophinomas (2/4) and non-functional tumours (4/15). In non-invasive adenomas, protein accumulation was observed only in ACTH-secreting tumours where 50% were positive (16/32). No protein accumulation was identified in any control tissue. These results indicate that p53 protein accumulation may play a role in the development of Cushings adenomas and in the progression of non-functional tumours to the invasive state.

Adenoma↗
PubMed1995

P53 protein accumulates in Cushings adenomas and invasive non-functional adenomas.

The p53 protein, a negative regulator of cell growth, plays an important role in the pathogenesis of many human tumours following gene mutation and/or deletion. We screened a large number of sporadic pituitary tumours for p53 protein accumulation suggestive of gene mutation. Samples were divided into benign adenomas (n = 95) and invasive tumours with local or distant invasion (n = 26). All main tumour classes were represented. Putative p53 mutations were detected by immunohistochemistry on paraffin-embedded sections using polyclonal CM-1 and monoclonal DO-7 and PAb1801 antibodies. Results were compared to normal post-mortem pituitary tissue controls (n = 17). p53 protein accumulation was detected in invasive tumours (16%), but only in corticotrophinomas (2/4) and non-functional tumours (4/15). In non-invasive adenomas, protein accumulation was observed only in ACTH-secreting tumours where 50% were positive (16/32). No protein accumulation was identified in any control tissue. These results indicate that p53 protein accumulation may play a role in the development of Cushings adenomas and in the progression of non-functional tumours to the invasive state.

Adenoma↗
PubMed1994

Serous oligocystic and ill-demarcated adenoma of the pancreas: a variant of serous cystic adenoma.

Serous cystic tumours of the pancreas are uncommon and are usually classified as microcystic adenomas (MCA). As new types of serous cystic tumours of this organ have been reported we reviewed a series of 14 lesions and from macroscopic findings two groups were distinguished: ten tumours revealed the features of MCA, while four were clearly distinct from MCA. Grossly, the latter tumours showed only few cysts which were irregularly assembled in fibrous stroma. On the cut surface, there was neither a central stellate scar nor a circumscribed tumour border, features characterizing MCA. Microscopically, the cysts were lined by cuboidal, non-mucin-producing cells. Immunocytochemical staining for cytokeratins 7, 8, 18 and 19 revealed a ductal phenotype. All non-MCA were found in the head of the pancreas and three of them occurred in men. There were no tumour recurrences or signs or malignant transformation after resection (mean follow-up, 2.9 years). These results suggest that there are serous cystic tumours distinct from MCA which may represent another variant of the category of serous cystic adenomas of the pancreas. We propose the term serous oligocystic and ill-demarcated adenoma (SOIA) for these tumours. It is possible that the recently described macrocystic sybtype of serous cystadenoma and SOIA and variants of the same tumour.

Adenoma↗
PubMed1987

A rare case of Maffucci's syndrome combined with tuberculum sellae enchondroma, pituitary adenoma and thyroid adenoma.

Maffucci's syndrome is a rare, congenital mesodermal dysplasia combined with dyschondroplasia and haemangiomatosis, and there are only about 150 reported cases. This syndrome is often combined with other neoplasms. Our case was associated with goitre, enchondroma of the tuberculum sellae and pituitary adenoma; the latter brought about disturbance of vision. Including ours, four cases of Maffucci's syndrome associated with pituitary adenoma are found in the literature. In the case of Maffucci's syndrome, it is necessary to examine associated disease as well as associated pituitary adenoma and skull base enchondroma, similar to the correlation of von Recklinghausen's disease with acoustic neurinoma.

Adenoma↗
PubMed2005

Adenoma with gastric differentiation (so-called pyloric gland adenoma) in a heterotopic gastric corpus mucosa in the rectum.

In a 46-year-old man, a pedunculated rectal polyp measuring 3.0x3.0x2.0 cm was diagnosed histologically as a pyloric gland-type adenoma arising in heterotopic gastric corpus mucosa. The luminal site was covered by glands of the gastric foveolar type, displaying focal marked proliferation interpreted as low-grade intraepithelial neoplasia. A bidirectional gastric differentiation was found: most lower glandular structures showed positivity for the deep gastric mucin core protein Muc 6 and superficial positivity for gastric foveolar epithelium mucin core protein Muc 5AC. Pyloric gland adenoma has so far been described in one larger series only and a few case reports of the stomach, gallbladder, pancreatic duct and within heterotopic gastric corpus mucosa of the duodenal bulb. The present case report is the first case of a pyloric gland-type adenoma within a gastric corpus heterotopia of the rectal mucosa.

Adenoma↗
PubMed2006

Diagnostic accuracy of chemical-shift MR imaging to differentiate between adrenal adenomas and non adenoma adrenal lesions.

PURPOSE: The objective of this study was to evaluate the diagnostic accuracy of chemical-shift (CS) magnetic resonance (MR) imaging in the differential diagnosis of adenoma and nonadenoma adrenal masses. MATERIALS AND METHODS: We enrolled 36 patients (9 men, 27 women, mean age 51.3+14.4 years) with unilateral (n=31) or bilateral (n=5) adrenal masses incidentally discovered during imaging examinations [ultrasound (US), computed tomography (CT)] performed for other indications. A total of 41 adrenal lesions were evaluated (mean diameter 3.0+2.2 cm). Histology (n=19), biopsy (n=3) or clinical-imaging follow-up (n=19) demonstrated 29 adenomas, five pheochromocytomas, three cysts and four carcinomas. MR imaging was performed using the following breath-hold sequences: T1-fast field echo (FFE) [repetition time (TR)/echo time (TE)=236/4.6 ms], T2-turbo spin echo-single shot (TSE-SSh) (TR/TE=831/80 ms), T1-DUAL-FFE (TR=236, double TE=4.6/2.3 ms in phase and out of phase) and T1-FFE after gadolinium-DTPA (Gd). Axial and coronal imaging planes were used, with a slice thickness of 3-5 mm. MR images were qualitatively assessed for signal intensity of the adrenal mass relative to the liver on T1, T2, CS and T1-Gd scans; diagnostic criteria for adenomas were isointensity or hypointensity on both T1 and T2 scans, out-of-phase CS signal loss and mild transient enhancement after Gd. RESULTS: Analysis of T1-T2 signal intensity showed diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 80%, 72%, 100%, 100% and 60%, respectively. In contrast, analysis of CS and T1-Gd signal intensity showed diagnostic accuracy, sensitivity, specificity, PPV and NPV for both sequences of 93%, 90% (p<0.05 vs. T1-T2 analysis), 100%, 100% and 80% (p<0.05 vs. T1-T2 analysis), respectively. CONCLUSIONS: CS MR imaging significantly improves characterization of adrenal masses compared with conventional T1-T2-weighted images, providing accuracy similar to that of the T1 sequence after Gd. Therefore, the CS sequence is strongly recommended for MR study of adrenal masses, and its use might obviate the need for Gd administration.

Adrenal Cortex Neoplasms↗
PubMed1992

Trabecular and solid-cribriform types of basal cell adenoma. A morphologic study of two cases of an unusual variant of monomorphic adenoma.

Monomorphic adenomas are a morphologically complex group of salivary gland tumors. Two unusual examples, one a trabecular and the other a solid form of basal cell adenoma, reveal the development of a cribriform growth pattern focally in the former example and diffusely in the latter. They illustrate the potential for cellular differentiation within this subgroup, organization of synthetic products by the tumor cells, and the histologic criteria useful for the distinction of basal cell adenoma from adenoid cystic carcinoma.

Adenoma↗