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PubMed2001

Focal nodular hyperplasia and hepatocellular adenoma of the liver: differentiation with multiphasic helical CT.

OBJECTIVE: Differences of attenuation and enhancement patterns in focal nodular hyperplasia and hepatocellular adenoma were evaluated and quantified using triphasic single-slice helical CT. MATERIALS AND METHODS: Forty-five histologically proven focal nodular hyperplasias in 27 patients and 18 hepatocellular adenomas in six patients were examined with helical CT. Quantitative evaluation included the following: attenuation of lesions, scar, and liver parenchyma during unenhanced, arterial (20 sec after injection), and portal venous phases (70 sec after injection); relative enhancement of lesions and liver (the ratio between attenuation in arterial phase and portal venous phase, respectively, and attenuation in unenhanced phase); and the prevalence of scar and its central vessel in focal nodular hyperplasia. RESULTS: The study showed no significant difference between mean attenuation values of focal nodular hyperplasia (mean +/- SD, 51.2 +/- 5.9 H) and hepatocellular adenoma (mean +/- SD, 56.3 +/- 7.8 H) in the unenhanced phase. In the arterial phase attenuation values were significantly higher in focal nodular hyperplasia (mean +/- SD, 117.9 +/- 15.1 H) than in hepatocellular adenoma (mean +/- SD, 80.1 +/- 10.5 H). In the portal venous phase no significant differences in attenuation values were detected between focal nodular hyperplasia (mean +/- SD, 112.1 +/- 20.4 H) and hepatocellular adenoma (mean +/- SD, 110.2 +/- 12.9 H). For enhancement parameter thresholds separating focal nodular hyperplasia from hepatocellular adenoma, the following were found: the relative enhancement was higher in 100% of the focal nodular hyperplasias and lower than or equal to 1.6 (accuracy, 96%) in 87% of the hepatocellular adenomas. CONCLUSION: Triphasic helical CT combined with quantitative evaluation of liver lesions offers the possibility of detecting differences in liver lesions that are visually similar on CT. The attenuation and relative enhancement in the arterial phase show significant differences that make accurate differentiation between focal nodular hyperplasia and hepatocellular adenoma possible.

Adenoma, Liver Cell↗
PubMed1997

Epithelial hyperplasia of the extra-glandular excretory ducts of human minor salivary glands: a histopathologic study.

The histologic features of normal and hyperplastic epithelia of the extra-glandular excretory ducts of human minor salivary glands were studied, and their pathologic significance evaluated. Normal duct epithelium consisted of two layers: inner columnar cells, and basal cubical or squamous cells. A few goblet cells were present among the inner cells. Hyperplasia of the duct epithelia occurred focally or entirely, and was classified into the following histologic types: (1) simple hyperplasia, and (2) metaplastic hyperplasia, which were divided into (a) mucous cell hyperplasia, (b) oncocytic hyperplasia and (c) squamous cell hyperplasia. Squamous cell hyperplasia was subdivided into (i) acanthotic type and (ii) reserve cell-like type with or without dysplasia. Simple or metaplastic epithelial hyperplasia of the extra-glandular excretory ducts of minor salivary glands may be induced by chronic inflammation or other types of irritation, and proliferating cells of such regenerating tissue sometimes exhibit features reminiscent of a neoplastic process. Furthermore, it is suggested that metaplastic epithelial hyperplasia of the excretory minor salivary gland ducts could be the site of origin of tumor development, i.e., some oral squamous cell carcinomas may arise from primary lesions in the hyperplastic epithelium of the extraglandular excretory minor salivary gland ducts.

Carcinoma, Squamous Cell↗
PubMed1999

[Incidence of benign prostatic hyperplasia and hepatic cirrhosis].

We studied the incidence of benign hyperplasia of the prostate and hepatic cirrhosis in an ambulatory cohort. Undisturbed androgen production is one of the prerequisites for the development of benign prostatic hyperplasia. The disturbed metabolic activity of the cirrhotic liver causes often hypoandrogenism. Therefore a decreased incidence of prostatic hyperplasia is expected for patients with cirrhosis. All male patients of european origin over 40 newly admitted for treatment at the medical outpatient clinic in Zürich during a period of 6 months were enrolled. From a cohort of 2038 males over 40 a benign prostatic hyperplasia was diagnosed in 124. Nine had cirrhosis of the liver. In 6 patients cirrhosis was found in addition to benign prostatic hyperplasia. The study also confirmed an increased incidence of benign prostatic hyperplasia with age. The incidence of cirrhosis, however, decreased with age in our study, probably as a consequence of reduced life expectancy of the cirrhotic patient. The combined incidence of benign prostatic hyperplasia and hepatic cirrhosis became less common with age than benign prostatic hyperplasia alone. This corresponded to our expectations. This collection of epidemiologic data on benign prostatic hyperplasia and hepatic cirrhosis disclosed several difficulties that should be considered for future studies.

Adult↗
PubMedDate not supplied

Differential diagnosis of endometrial hyperplasia and carcinoma by computerized image cytometry of cell proliferation, apoptosis and Bcl-2 expression.

BACKGROUND: The differential diagnosis between atypical endometrial hyperplasia and endometrial carcinoma is often difficult and based on controversial criteria. Cell kinetic parameters may be helpful. DESIGN: Cell proliferation, apoptosis and Bcl-2 expression were evaluated in benign endometrium, non atypical and atypical endometrial hyperplasia and endometrial carcinoma. The results were compared by one way analysis of variance and Bonferroni T tests. RESULTS: Cell proliferation was significantly higher (p < 0.01) in endometrial adenocarcinoma (25.6 percent) than in atypical hyperplasia (17.1 percent) and non-atypical hyperplasia (7.5 percent) of the endometrium. Apoptosis was observed in 12.3 percent of endometrial adenocarcinomas and less frequently in atypical hyperplasia (7.4 percent) and non-atypical hyperplasia of the endometrium (5.8 percent). Bcl-2 expression was significantly lower (p < 0.002) in endometrial adenocarcinoma (1.7 percent) than in atypical hyperplasia (4.2 percent) and non-atypical hyperplasia (5.3 percent) of the endometrium. In benign endometrium, cell proliferation and Bcl-2 expression were significantly higher during the proliferative phase while the rate of apoptosis was significantly higher during the secretory phase. CONCLUSIONS: Our data suggests that cell proliferation, apoptosis and Bcl-2 expression could be helpful when distinguishing endometrial carcinoma from non-atypical or atypical endometrial hyperplasia.

Adult↗
PubMed2000

Nuclear volume estimates in prostatic atypical adenomatous hyperplasia.

OBJECTIVE: To investigate nuclear volume estimates by the point-sampled intercepts method in atypical adenomatous hyperplasia (AAH) as compared with nodular hyperplasia and well-differentiated prostatic adenocarcinoma. STUDY DESIGN: The study group consisted of 27 formalin-fixed, paraffin-embedded, whole-mounted radical prostatectomy specimens that contained foci of nodular hyperplasia, atypical adenomatous hyperplasia and well-differentiated adenocarcinoma (Gleason pattern 1 and 2). Representative sections were selected for stereologic estimation of volume-weighted mean nuclear volume by the point-sampled intercepts method. On each focus, an average of five fields of vision were systematically chosen. RESULTS: The quantitative results indicate an increase in nuclear volume from nodular hyperplasia (209 +/- 65 micron 3) to AAH (237 +/- 85 micron 3) and prostate adenocarcinoma (436 +/- 106 micron 3). Significant differences were found (F = 39.0, P < .001) with two group comparisons (Scheffe's procedure) between prostate cancer and AAH (P < .001) or nodular hyperplasia (P < .001). The difference between AAH and benign hyperplasia was not signifcant. CONCLUSION: The results indicate that three-dimensional estimates of the nuclear size discriminate AAH and nodular hyperplasia from well-differentiated prostate adenocarcinoma. These findings suggest that AAH is probably a histologic variant of benign prostatic hyperplasia the exact relationship of which to prostatic adenocarcinoma remains to be determined.

Adenocarcinoma↗
PubMed2003

Ovarian stromal hyperplasia and ovarian vein steroid levels in relation to endometrioid endometrial cancer.

OBJECTIVE: To study the relationship between the presence of endometrioid endometrial cancer, the degree of ovarian stromal hyperplasia and ovarian steroid production in postmenopausal women. DESIGN: Retrospective and prospective study, respectively. SETTING: Medical Centre Leeuwarden and the University Hospital Groningen, The Netherlands. Postmenopausal women with or without endometrial cancer, undergoing a hysterectomy with bilateral salpingo-oophorectomy. METHODS: In 112 women with endometrioid endometrial cancer, 47 women with a benign gynaecological condition and 10 women with non-endometrioid endometrial cancer, the degree of ovarian stromal hyperplasia was scored retrospectively on a semi-quantitative scale (atrophy, slight, marked). All women were postmenopausal and had undergone a hysterectomy with bilateral salpingo-oophorectomy. Prospectively, blood sampling from the ovarian veins was performed in a further 60 women. Steroid levels (oestrone, oestradiol, androstenedione, testosterone) were determined and related to the degree of ovarian stromal hyperplasia and the presence (n = 52) or absence (n = 8) of endometrioid endometrial cancer. MAIN OUTCOME MEASURES: Degree of ovarian stromal hyperplasia and steroid levels in the utero-ovarian circulation. RESULTS: In the retrospective study, the degree of ovarian stromal hyperplasia was higher in the presence of endometrioid endometrial cancer (P = 0.0001). The prospective study showed that an increasing degree of ovarian stromal hyperplasia was related to higher ovarian levels of both testosterone and androstenedione (P < 0.05 and P < 0.005, respectively), but not to oestrone or oestradiol. A non-significant increase in mean ovarian vein levels of both testosterone and androstenedione was seen in patients with endometrial cancer as compared with patients with benign conditions. CONCLUSION: In endometrioid endometrial cancer, higher degrees of ovarian stromal hyperplasia were found and with increasing degrees of ovarian stromal hyperplasia, levels of ovarian vein androgens were higher. A causal relationship in the origin of hormone-dependent endometrial pathology may exist between ovarian stromal hyperplasia, ovarian vein androgen levels and endometrioid endometrial carcinoma.

Androstenedione↗
PubMedDate not supplied

[Unilateral facial and cerebral hyperplasia associated with neurofibromatosis type 1. Report of four patients].

INTRODUCTION: Plexiform neurofibroma in any location is one of the commonest complications associated with neurofibromatosis type 1 (NF1). Plexiform neurofibroma of the upper eyelid and orbit is usually associated with ipsilateral hemifacial hyperplasia. We present four patients with NF1 and plexiform neurofibroma of the eyelid and orbit associated with hemifacial hyperplasia, who also showed hyperplasia of the unilateral cerebral hemisphere. CASE REPORTS: There are four patients, three females and one male, who consulted because of NF1 with plexiform neurofibroma of upper eyelid and hemifacial hyperplasia. Upper eyelid involvement was observed since birth and progressed during the first years of life. The patients showed normal neurological and mental development without motor or cerebellar disorders. Magnetic resonance studies demonstrated the asymmetric hyperplasia of the ipsilateral hemisphere in all four cases and of the cerebellar hemisphere in one case. The degree of hemispheric hyperplasia was related to the size and extension of the plexiform neurofibroma, as well as to the severity of the hemifacial hyperplasia. In our case which had the plexiform neurofibroma extended to the neck and the upper thorax, the hyperplasia not only affected the cerebral hemisphere but also the ipsilateral cerebellar hemisphere. All parts of the hemisphere showed increased size. The cortex of the entire hemisphere showed normal differentiation of the subcortical white matter. CONCLUSION: NF1 appears to be related with facial and cerebral ipsilateral hemihyperplasia. The relation between the size and extension of the orbital, eyelid and facial plexiform neurofibroma and the degree of asymmetry of the hemispheric hyperplasia suggest that different influences of a still unknown agent, possibly a gene, obviously related to NF1, causes both the intracranial and extracranial abnormalities.

Adolescent↗
PubMed1983

[Cytological findings on endometrial carcinoma and endometrial hyperplasia].

The usefulness of endometrial cytology was studied for the purpose of early diagnosis of endometrial carcinoma in 423 patients. In the cytological examination, 15 patients were either "suspicious" or "positive". Histological findings revealed adenomatous hyperplasia in 6, atypical hyperplasia in 3 and endometrial carcinoma in 3 patients. All of these patients with positive histological findings had "suspicious" or "positive" in cytological examination. None had false negative. "Suspicious" or "positive" endometrial cytology was delineated in histologically positive lesions including endometrial carcinoma, atypical hyperplasia and adenomatous hyperplasia. Many cells with various acinous patterns were observed in patients with diseases more serious than atypical hyperplasia. The nuclei became larger and irregular in proportion to the progression of the lesion, though hypercytochromia of the nuclear chromatin was most marked in patients with adenomatous hyperplasia. There was a significant difference in the number of nucleoli between cells of adenomatous hyperplasia and those of atypical hyperplasia and endometrial carcinoma. Also, there was an apparent difference in the size and irregularity of the nucleoli between atypical hyperplasia and endometrial carcinoma. Phagocytosis of white blood cells was frequently observed in patients with endometrial carcinoma. Therefore, it is believed that endometrial cytology is useful not only in screening endometrial carcinoma and related diseases but also to some degree in the estimated diagnosis of these lesions.

Adenoma↗
PubMed1994

Increased expression of transforming growth factor beta isoforms and basic fibroblast growth factor in complex hyperplasia and adenocarcinoma of the endometrium: evidence for paracrine and autocrine action.

Endometrial carcinoma is associated with antecedent simple and complex hyperplasia, and the endometrium is a target tissue for the action of cytokines and growth factors. Transforming growth factor (TGF)-beta s are potent cellular growth and differentiation regulatory factors. Therefore, we investigated the potential role for TGF-beta s in the normal proliferative endometrium and its possible involvement in the transition to complex hyperplasia and progression to endometrial carcinoma. The angiogenic and mitogenic growth factor, basic fibroblast growth factor, was used for comparison. Differential TGF-beta isoform-specific immunoreactivity was observed in the normal endometrium, which is composed of glandular and stromal cells. There was an increase in TGF-beta 3 but not TGF-beta 1 or TGF-beta 2 in the glandular epithelium from the proliferative to the secretory phase of the menstrual cycle. Immunostaining for TGF-beta 2 was more intense in the stroma than the glands. In contrast, TGF-beta 1 and TGF-beta 3 were near equal intensity in these two endometrial compartments, TGF-beta 3 being the most intense. The glandular epithelium demonstrated a statistically significant stepwise increase in the expression of all three TGF-beta s progressing from the normal proliferative endometrium to simple hyperplasia and on to complex hyperplasia. However, the stromal cells maintained approximately the same level of immunoreactivity for TGF-beta in all these samples. In comparing proliferative endometrium with complex hyperplasia, there was a 5.1-, 3.4-, and 2.6-fold increase in immunostaining in the glands for TGF-beta 1, TGF-beta 2, and TGF-beta 3, respectively (P < or = 0.001). There was no further increase in immunoreactivity with progression from preneoplastic complex hyperplasia to carcinoma. Immunoreactive basic fibroblast growth factor was slight in normal endometrium and simple hyperplasia. There was a 4.6- and 4.2-fold increase in immunostaining observed in complex hyperplasia compared with proliferative endometrium in the glandular (P < or = 0.0054) and stromal (P < or = 0.0053) cells, respectively, with no further increase in carcinoma. By in situ hybridization, an increase in mRNA for all TGF-beta isoforms paralleled TGF-beta immunoreactivity. However, in contrast to the increased immunostaining in the glands in complex hyperplasia, there was remarkably more mRNA in the stromal cell compartment. The discordant expression of mRNA and protein was only observed in the pathological endometrium since both were more highly expressed in the stromal cells in normal proliferative endometrium.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1997

Risk of breast cancer associated with atypical hyperplasia of lobular and ductal types.

Epidemiological studies using the histological classification of Page for benign breast disease consistently demonstrate a positive association between atypical hyperplasia and the subsequent development of breast cancer. However, atypical hyperplasia is of either lobular or ductal types, and breast cancer risk in relation to type of atypical hyperplasia has not been studied extensively. Thus, we investigated prospectively the risk of breast cancer associated with histological subtypes of benign proliferative breast disease, including the types of atypical hyperplasia, among participants in the Nurses' Health Study who had biopsy-confirmed benign breast disease. Women who subsequently developed breast cancer were matched by year of birth and year of biopsy to participants who were free from breast cancer. Benign biopsy slides were classified according to the criteria of Page. Odds ratios (ORs) of breast cancer and 95% confidence intervals (CIs), adjusted for the matching variables and other breast cancer risk factors, were computed using unconditional logistic regression with benign nonproliferative breast disease as the referent group. Atypical ductal hyperplasia (OR = 2.4; 95% CI, 1.3-4.5) or atypical lobular hyperplasia (OR = 5.3; 95% CI, 2.7-10.4) in a prior biopsy were associated with increased breast cancer risk. Atypical lobular hyperplasia was more strongly associated with the risk of premenopausal breast cancer (OR = 9.6; 95% CI, 3.3-27.8) than with the risk of postmenopausal breast cancer (OR = 3.7; 95% CI, 1.3-10.2). The association of atypical ductal hyperplasia and breast cancer risk varied little by menopausal status. The magnitude of breast cancer risk seems to vary according to the type of atypical hyperplasia present at biopsy.

Adult↗
PubMed1998

[The role of hysteroscopy in the diagnosis and follow-up of endometrial hyperplasia].

BACKGROUND: Preneoplastic lesions of endometrium such as endometrial hyperplasia (simple and complex with or without cytological atypias) represent an important cause of abnormal uterine bleeding. Among diagnostic techniques, hysteroscopy presents several advantages: it is an out-patient procedure, minimally invasive, repeatable, of rapid execution and with low cost. The hysteroscopic pattern of endometrial hyperplasia appears with an over-development of the endometrial mucosa with increased glandular openings, increased vascularization, cystic dilatations, polypoid aspects. METHODS: Since October 1984 to January 1995 at the Gynecologic Endoscopic Service of Obstetrics and Gynecology Department of the University of Bologna, 13,438 hysteroscopies were performed: 291 (2.16%) in patients submitted to hysteroscopy for previous diagnosis of endometrial hyperplasia. The first diagnosis of endometrial hyperplasia was made in 125 (42.3%) patients through hysteroscopic biopsy, while for 166 patients (57.04%) the first diagnosis was made by endometrial curettage of VABRA. RESULTS: The results showed that the endometrial hyperplasia is typical in perimenopausal age and this finding is more frequently symptomatic. The histological diagnosis after hysteroscopy was: simple hyperplasia in 106 patients (84.8%), complex in 12 patients (9.6%) and atypical in 6 patients (4.8%). One case of simplex hyperplasia was associated with endometrial cancer (0.8%). The comparison between histological diagnosis and hysteroscopic diagnosis showed that agreement is reached in 113 cases (90.4%). However, it is to note that diagnostic agreement of complex hyperplasia cases was about 100%, but in 22 cases the hysteroscopic diagnosis was simplex hyperplasia rather than complex or atypical. The errors of hysteroscopy were observed in 10 cases (8%). CONCLUSIONS: The hysteroscopic diagnosis should not replace histological diagnosis, mostly in hysteroscopies performed after progestagen therapy, because the changes induced by drugs make more difficult the interpretation of hysteroscopy. However, hysteroscopy is complementary to histological analysis since permits a global evaluation of endometrial mucosa, directs biopsy on dishomogeneous areas and represents the only means to make diagnosis when biopsy is not practicable.

Adult↗
PubMed1990

Micronodular transformation (nodular regenerative hyperplasia) of the liver: a report of 64 cases among 2,500 autopsies and a new classification of benign hepatocellular nodules.

Nodular regenerative hyperplasia is defined by hepatocellular nodules distributed throughout the liver in the absence of fibrous septa between the nodules. Most reports have been single cases so that the prevalence and clinical significance of nodular regenerative hyperplasia is uncertain. In this study, the hepatic histology of 2,500 consecutive autopsies was reviewed. A spectrum of nodular transformation was found with nodular regenerative hyperplasia present in 2.6% of autopsy livers and qualitatively similar but lesser degrees of nodular transformation in a further 10.2%. Nodular transformation was also seen in 47% of livers with cirrhosis and 69% with incomplete cirrhosis. Obliteration of many small portal veins was seen in all cases with nodular regenerative hyperplasia, but only 4.7% of these had evidence of portal hypertension. The prevalence of various clinical states was compared in nodular regenerative hyperplasia and in controls. The results confirm, extend and quantify the spectrum of associated diseases. Nodular regenerative hyperplasia occurs in 5.6% of individuals over age 80 and with increased frequency in patients with systemic arteritis, polymyalgia rheumatica, massive tumor infiltration and mineral oil deposition. Nodular regenerative hyperplasia appears to be the hepatic analogue of arterial and arteriolar nephrosclerosis. A new classification of nodular transformation is proposed that encompasses the spectrum of lesions described here and the previously defined entities of focal nodular hyperplasia, partial nodular transformation and "cirrhosis telangiectasia hepatis." The major conclusion is that nodular regenerative hyperplasia is a secondary and nonspecific tissue adaptation to heterogeneous distribution of blood flow and does not represent a specific entity.

Aged↗
PubMed1976

Parathyroid hyperplasia in primary hyperparathyroidism: a review of 85 cases.

Parathyroid hyperplasia of all four glands was found to be the cause of primary hyperparathyroidism in 85 of 557 cases seen at the Massachusetts General Hospital between 1930 and 1973. There were 66 cases of chief cell hyperplasia and 19 cases of clear cell hyperplasia that were grossly, microscopically, and ultrastructurally distinct. Although the clinical findings overlap, there are several differences in the signs and symptoms between these two forms of hyperplasia. Both types are treated by subtotal removal of all the parathyroid tissue. Removal of insufficient tissue has left residual hyperparathyroidism in 45% of those with chief cell hyperplasia and 11% of those with clear cell hyperplasia after what was thought to be definitive surgery. Postoperative hypoparathyroidism was found in 15% of the patients with chief cell hyperplasia and in none with clear cell hyperplasia. These findings further suggest that removal of three and one-half glands in the more than 86% of patients with one gland involvement (adenoma or carcinoma) as the cause of primary hyperparathyroidism is unwarranted.

Adult↗
PubMed1989

Nodular regenerative hyperplasia of the liver following bone marrow transplantation.

Liver disease in the early period following bone marrow transplantation may be due to a number of causes, including pretransplant cytoreduction with chemotherapy and irradiation. Although the relationship of venoocclusive disease to these agents has been well established, another process, nodular regenerative hyperplasia, may also occur. In this retrospective study, we evaluated the incidence and clinical signs of these two processes as defined by histological criteria. In 103 patients studied, nine (8.8%) had venoocclusive disease and 23 (22.5%) had nodular regenerative hyperplasia. Venoocclusive disease was significantly associated with transplantation for malignancy other than acute or chronic leukemia and use of busulfan as a cytoreductive agent and occurred in younger patients. Nodular regenerative hyperplasia did not differ from the general transplant population in terms of underlying disease, cytoreductive regimen, graft vs. host disease prophylaxis or age. Both venoocclusive disease and nodular regenerative hyperplasia were associated with ascites. Venoocclusive disease had a poor prognosis, with eight of nine cases dying of or with venoocclusive disease, whereas no case of nodular regenerative hyperplasia died of liver disease and only 5 of 23 died with nodular regenerative hyperplasia. Using retrospective data, five of 11 patients fulfilling clinical criteria for the diagnosis of venoocclusive disease actually had nodular regenerative hyperplasia, as did all of nine patients fulfilling the criteria for "possible" venoocclusive disease. These results indicate that nodular regenerative hyperplasia is a process which occurs commonly following bone marrow transplantation and which may be clinically misdiagnosed as venoocclusive disease.

Bone Marrow Transplantation↗
PubMed2003

Frequent genetic alterations in flat urothelial hyperplasias and concomitant papillary bladder cancer as detected by CGH, LOH, and FISH analyses.

Flat urothelial hyperplasia, defined as markedly thickened urothelium without cytological atypia, is regarded in the new WHO classification as a urothelial lesion without malignant potential. Frequent deletions of chromosome 9 detected by fluorescence in situ hybridization (FISH) have been previously reported in flat urothelial hyperplasias found in patients with papillary bladder cancer. Using comparative genomic hybridization (CGH) and microsatellite analysis, these hyperplasias and concomitant papillary tumours of the same patients were screened for other genetic alterations to validate and extend the previous findings. Eleven flat hyperplasias detected by 5-ALA-induced fluorescence endoscopy and ten papillary urothelial carcinomas (pTaG1-G2) from ten patients were investigated. After microdissection, the DNA of the lesions was pre-amplified using whole genome amplification (I-PEP-PCR). Loss of heterozygosity (LOH) analyses were performed with five microsatellite markers at chromosomes 9p, 9q, and 17p. CGH was performed using standard protocols. In 6 of 11 hyperplasias and 7 of 10 papillary tumours, deletions at chromosome 9 were simultaneously shown by FISH, LOH, and CGH analyses. There was a good correlation between FISH, LOH, and CGH analyses, with identical results in 6 of 10 patients. In addition to deletions at chromosome 9, further genetic alterations were detected by CGH in 9 of 10 investigated hyperplasias, including changes frequently found in invasive papillary bladder cancer (loss of chromosomes 2q, 4, 8p, and 11p; gain of chromosome 17; and amplification at 11q12q13). There was considerable genetic heterogeneity between hyperplasias and papillary tumours, but a clonal relationship was suggested by LOH and/or CGH analyses in 5 of 10 cases. These data support the hypothesis that flat urothelial hyperplasias can display many genetic alterations commonly found in bladder cancer and could therefore be an early neoplastic lesion in the multistep development of invasive urothelial carcinoma.

Aged↗
PubMed2002

Microsatellite instability, MLH1 promoter methylation, and loss of mismatch repair in endometrial cancer and concomitant atypical hyperplasia.

OBJECTIVE: MLH1 methylation is associated with the microsatellite instability (MSI) phenotype in endometrial cancer and atypical endometrial hyperplasia, a premalignant precursor to carcinoma. The observation that methylation is also seen in atypical endometrial hyperplasia without MSI suggests that methylation is an early event in endometrial tumorigenesis. Our objective was to determine if methylation is always present in MSI-positive atypical hyperplasia concomitant with MSI-positive, methylation-positive carcinoma. METHODS: We used laser capture microdissection to study MLH1 methylation and MSI in a large series of endometrial cancer cases that had previously been shown to have methylation and the MSI-high (MSI-H) phenotype. We resampled areas of carcinoma from 27 patients along with 51 foci of concomitant atypical endometrial hyperplasia. RESULTS: Consistent with previous reports, we saw MLH1 methylation in areas of atypical endometrial hyperplasia that did not show MSI. In addition, we noted that 18% of the MSI-H atypical endometrial hyperplasia DNAs lacked methylation of critical cytosines in the MLH1 promoter. Immunohistochemistry studies showed that these MSI-H unmethylated foci of atypical endometrial hyperplasia failed to express MLH1, as did regions of simple hyperplasia. CONCLUSION: Methylation of the MLH1 promoter is an early event in endometrial tumorigenesis. Given that not all MSI-positive tissues had methylation at cytosines -229 and -231, it appears that methylation may not be required for MLH1 silencing and loss of mismatch repair.

Adaptor Proteins, Signal Transducing↗
PubMed1983

Pituitary hyperplasia. Definition, light and electron microscopical structures and significance in surgical specimens.

Surgical specimens of 15 normal and 106 para-adenomous anterior pituitaries were studied immunocytochemically and in part electron microscopically for the presence of hyperplasia. GH cell hyperplasia was found in 13% of all normal pituitaries, in 6% of the cases with Prolactin secreting adenomas and in 9% of the cases with ACTH secreting adenomas. Prolactin cell hyperplasia occurred in nearly equal percentages (17-23%) in normal pituitaries and in areas adjacent to GH-, Prolactin- or ACTH-secreting adenomas or adjacent to inactive adenomas. Previous findings of relatively more frequent Prolactin cell hyperplasia occurring together with Prolactin producing adenomas have to be revised. Prolactin cell hyperplasia as a primary source of hyperprolactinemia is very rare and almost always occurs in conjunction with oncocytic adenomas. ACTH cell hyperplasia was found in 13% of the normal pituitaries, in 14% of the cases with Prolactin secreting adenomas, in 58% of the cases with ACTH producing adenomas and in 40% of the pituitaries with GH secreting adenomas. We have no explanation for the latter result. ACTH cell hyperplasia may be the primary cause of Cushing's disease (18% of all Cushing cases). Hyperplasia of TSH cells in normal pituitaries was rare (7%) and with the exception of Prolactin producing adenomas (22%) was not found near adenomas. Clinical-pathological correlations are discussed.

Adrenocorticotropic Hormone↗
PubMed1996

Clonal analysis of nodular parathyroid hyperplasia in renal hyperparathyroidism.

Although it is well known that chronic renal failure induces parathyroid hyperplasia, the pathogenesis and development of this parathyroid lesion in this disease are poorly understood. Histopathologically, there is progression from diffuse to nodular hyperplasia, and each nodule consists of a single cell type with aggressive proliferative potential. Pathophysiologic and clinical investigations have suggested that neoplastic tumors may emerge from nodular hyperplasia. In this study the clonality of parathyroid tissue in nodular and diffuse hyperplasia in renal hyperparathyroidism was analyzed by a method based on restriction fragment length polymorphism of the X chromosome-linked phosphoglycerokinase gene and on random inactivation of the gene by methylation. DNA of peripheral lymphocytes was screened in 43 women undergoing parathyroidectomy for advanced renal hyperparathyroidism, and 10 of these patients appeared to be heterozygous. Fourteen specimens from these patients were available for clonal analysis. The analysis showed that all four specimens of diffuse hyperplasia were polyclonal, whereas all seven specimens from nodules in nodular hyperplasia and all three samples representing parathyroid tissue removed from forearm because of graft-dependent recurrence were revealed to be monoclonal. It is likely that the clonal origin of each nodule is independent. These results suggest that in renal hyperparathyroidism parathyroid glands initially grow diffusely and polyclonally, and then the cells in the nodules are later transformed monoclonally and proliferate aggressively. From the present study it can be concluded that nodular hyperplasia represents monoclonal parathyroid neoplasia, which might explain why patients with nodular hyperplasia in renal hyperparathyroidism are refractory to medical treatment, requiring parathyroidectomy. To prevent recurrences, nodular hyperplastic tissue should not be left at surgery.

Adult↗