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PubMed1990

A comparison of the results of long-term follow-up for atypical intraductal hyperplasia and intraductal hyperplasia of the breast.

Follow-up information was obtained on 199 women with breast biopsy specimens containing intraductal epithelial proliferation. The proliferations were divided into regular or ordinary intraductal hyperplasia (IDH) (117 cases) and atypical intraductal hyperplasia (AIDH) (82 cases). The average length of follow-up was 14 years for the patients with IDH and 12.4 years for the patients with AIDH. Of the 117 patients with ordinary IDH, carcinoma subsequently developed in six (5%); three of these were invasive carcinomas (2.6%). All three invasive carcinomas were in the ipsilateral breast, but of the three intraductal carcinomas (IDCa), two were in the contralateral breast. Of the 82 patients with AIDH, invasive carcinoma subsequently developed in eight (9.8%); six of these were located in the ipsilateral breast and two in the contralateral breast. One of these six patients died of disseminated carcinoma. The average interval to the subsequent carcinoma (intraductal and invasive carcinoma) was about the same in the two groups (8.3 years for AIDH and 8.8 years for IDH lacking atypia). When considering only subsequent invasive carcinomas, the interval was 8.3 years for the AIDH and 14.3 years for the IDH lacking atypia. Of the 14 patients with IDH and a family history of breast carcinoma, invasive carcinoma subsequently developed in one (7%) as compared with two (2%) of the 91 with a negative family history. Among patients with AIDH, invasive carcinoma subsequently developed in two of the 13 (15%) of those with a family history of breast carcinoma as compared with one of 57 (1.8%) of the women with a negative family history. The presence of atypia in epithelial hyperplasia is a significant factor in increasing the likelihood of the development of subsequent invasive carcinoma (P = 0.03; two-tailed test). Of women with AIDH, invasive carcinoma subsequently developed in 17% of those with sclerosing adenosis (SA) as compared with 4.2% of those without it. Therefore, SA may be a contributing factor to increased risk. A positive family history also appears to increase the likelihood of the subsequent development of invasive carcinoma, particularly in patients with AIDH.

Adolescent↗
PubMed2002

Usual ductal hyperplasia of the breast is a committed stem (progenitor) cell lesion distinct from atypical ductal hyperplasia and ductal carcinoma in situ.

Current classification systems in proliferative mammary gland pathology are based on a two-cell system, recognizing only glandular and myoepithelial lines of differentiation. A third cell type has recently been characterized in normal breast tissue by double-immunofluorescence analysis to express cytokeratin 5 (Ck5) only. These cells were shown to represent progenitor or adult stem cells that give rise to the glandular and myoepithelial cell lineage. The double-labelling technique has been applied to characterize a spectrum of intraductal epithelial proliferations, namely benign usual ductal hyperplasia, atypical ductal hyperplasia, and ductal carcinoma in situ, all of which are thought to represent the gradual steps of a sequence in the development of breast cancer. Immunofluorescence studies with specific antibodies against Ck5, Ck8/18/19, and smooth muscle actin were complemented by western blotting analysis of Ck5 and Ck8/18/19 expression in normal breast tissue and in proliferative lesions. Usual ductal hyperplasia appears to be a Ck5-positive committed stem (progenitor) cell lesion with the same differentiation potential as seen in the normal breast. This is in sharp contrast to atypical ductal hyperplasia/ductal carcinoma in situ, which display the differentiated glandular immunophenotype (Ck8/18/19-positive, but Ck5-negative). These data require the abandonment of the idea of an obligate biological continuum of intraductal proliferations from benign to malignant. This study provides evidence that cells undergoing malignant transformation tend to be fairly advanced in the glandular lineage of differentiation. The committed stem (progenitor) cell model may contribute to a better understanding of both benign proliferative breast disease and breast cancer development.

Blotting, Western↗
PubMed1982

Erythrocytosis, glomerulomegaly, mesangial hyperplasia, sialyl hyperplasia, and arteriosclerosis induced in rats by nickel subsulfide.

Histopathological examinations were performed upon groups of male Fischer rats killed at intervals from 1 h to 18 weeks after unilateral intrarenal (ir) injection of nickel subsulfide (2.5 or 5 mg of Ni3S2/rat). Consistent with previous findings, erythroid hyperplasia of bone marrow and spleen occurred from 2 to 18 weeks after Ni3S2-treatment, resulting in pronounced erythrocytosis. Hitherto unreported effects of Ni3S2-treatment include: (a) marked glomerulomegaly and hyperplasia of mesangial cells in both kidneys; (b) hyperplasia of submandibular salivary glands, and (c) widespread arteriosclerotic lesions. The present study suggests that mesangial cells of renal glomeruli produce erythropoietin. Discovery that ir injection of Ni3S2 induces arteriosclerotic lesions in rats furnishes a new experimental model to investigate the pathogenesis of arteriosclerosis.

Animals↗
PubMed1987

Thymic hyperplasia. I. True thymic hyperplasia. Review of the literature.

The condition of true thymic hyperplasia is defined as an increase of both size and weight of the gland while it maintains normal microscopic architecture. It occurs in three different clinicopathologic forms: True thymic hyperplasia without any other disease is extremely rare and only seven well documented examples could be found in a review of the literature. Enlargement of the thymus gland is reported as a form of rebound phenomenon in a number of conditions like recovery from severe stress situations, after administration of steroids, and after treatment of malignant tumors. Finally, thymic hyperplasia has been described in association with endocrine abnormalities, sarcoidosis, and Beckwith-Wiedeman syndrome.

Child↗
PubMed1989

A comparative morphometric and cytophotometric study of endometrial hyperplasia, atypical hyperplasia, and endometrial carcinoma.

The DNA content and nuclear measurements of five groups of endometrial proliferations--proliferative endometrium (PE), simple hyperplasia (SH), atypical hyperplasia (AH), well-differentiated carcinoma (WDC), and poorly differentiated carcinoma (PDC)--were compared using 14 descriptors in a stepwise discriminant analysis. Classification using the discriminant rules agreed with the pathologic interpretation for 78% of the specimens. All PEs were assigned to the correct group, and 97% of benign endometria and carcinomas were correctly classified as benign or malignant. Only two of 39 hyperplasias (5%) were misclassified as malignant, and only one of 36 carcinomas was classified as benign. In the difficult distinction between AH and WDC, using all descriptors for the five groups, only 68% of the AH and 60% of the WDC classifications were in agreement with the pathologist of record. However, when discriminant rules addressing only AH and WDC were used, 37 of 39 AHs and WDCs were in concordance. This suggests that a morphometric distinction between AH and WDC is feasible.

Carcinoma↗
PubMed1996

The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group.

BACKGROUND: Men with benign prostatic hyperplasia can be treated with alpha 1-adrenergic-antagonist drugs that relax prostatic smooth muscle or with drugs that inhibit 5 alpha-reductase and therefore reduce tissue androgen concentrations. However, the effects of the two types of drugs have not been compared. METHODS: We compared the safety and efficacy of placebo, terazosin (10 mg daily), finasteride (5 mg daily), and the combination of both drugs in 1229 men with benign prostatic hyperplasia. American Urological Association symptom scores and peak urinary-flow rates were determined at base line and periodically for one year. RESULTS: The mean changes from base line in the symptom scores in the placebo, finasteride, terazosin, and combination-therapy groups at one year were decreases of 2.6, 3.2, 6.1, and 6.2 points, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). The mean changes at one year in the peak urinary-flow rates were increases of 1.4, 1.6, 2.7, and 3.2 ml per second, respectively (P<0.001 for the comparisons of both terazosin and combination therapy with finasteride and with placebo). Finasteride had no more effect on either measure than placebo. In the placebo group, 1.6 percent of the men discontinued the study because of adverse effects, as did 4.8 to 7.8 percent of the men in the other three groups. CONCLUSIONS: In men with benign prostatic hyperplasia, terazosin was effective therapy, whereas finasteride was not, and the combination of terazosin and finasteride was no more effective than terazosin alone.

Adrenergic alpha-Antagonists↗
PubMed1992

Histopathological and immunohistochemical study of atypical lymphoid hyperplasia and benign lymphoid hyperplasia of the stomach.

We propose dividing histologically reactive lymphoid hyperplasia (RLH) of the stomach into two categories: atypical lymphoid hyperplasia (ALH), characterized by abnormal follicular architecture and infiltration of atypical lymphoid cells, and benign lymphoid hyperplasia (BLH), where normal follicular patterns are preserved and no atypical cells are found. Using twenty RLH cases (10 ALHs and 10 BLHs), both categories were compared from histopathological and immunohistochemical aspects. Macroscopic division into superficial, thick-walled and nodular types revealed most ALH (80%) to be superficial in character whereas in BLH superficial and thick-walled types were almost equally represented. Lesion size tended to be larger in ALH (greater than 6.1 cm) than in BLH (6.0 cm greater than) cases. As for prognosis after gastrectomy, both categories were favorable. On immunohistochemistry, ALH tended to be strongly labeled by B lymphocyte markers as compared to BLH, where only a weakly positive reaction was expressed. Infiltration of cells labeled by T lymphocyte markers was less conspicuous in ALH than in BLH. From these data, we concluded that ALH and BLH are two distinctive categories of lesion and that ALH has characteristics similar to these demonstrated by malignant lymphoma.

Female↗
PubMed1990

Adrenal medullary hyperplasia. Hyperplasia-pheochromocytoma sequence.

We present a case of unilateral adrenal medullary hyperplasia in a 63-year-old woman with clinical signs and symptoms of pheochromocytoma unassociated with multiple endocrine neoplasia. The surgically removed adrenal gland revealed diffuse medullary hyperplasia with multiple micronodules measuring up to 2 mm. The micronodules were composed of enlarged chromaffin cells with atypia, histologically similar to those of pheochromocytoma, forming small solid alveolar patterns separated by a fibrovascular stroma. Removal of the hyperplastic adrenal gland resulted in disappearance of paroxysmal nocturnal hypertension and palpitation. These results suggest that diffuse and nodular medullary hyperplasia is the precursor of pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1986

Nodular regenerative hyperplasia and focal nodular hyperplasia of the liver associated with severe cholestasis. Report of a case with autopsy findings.

Nodular regenerative hyperplasia of the liver was found at liver biopsy and at autopsy in a 61-year-old woman with severe cholestasis. Increased bilirubin levels persisted over a follow-up period of 4 years. Microscopic findings included hyperplastic hepatocytic nodules, interlobular bile duct lesions, fibrous medial and intimal thickening of small arterial branches and portal veins, and recanalization of a thrombus in a major portal branch related to an area of focal nodular hyperplasia of the liver. Bile duct and small vessel changes were prominent in the present case. Their role as contributing factors to the development of nodular regenerative hyperplasia of the liver is discussed.

Atrophy↗
PubMed1994

[Cushing's syndrome due to huge bilateral adrenocortical multinodular hyperplasia--ACTH-independent bilateral adrenocortical macronodular hyperplasia(AIMAH)].

Six cases with ACTH-independent bilateral adrenocortical macronodular hyperplasia (AIMAH) were presented, and 21 reported cases were reviewed. Bilateral adrenal glands in AIMAH were greater than those in any other subtype of nodular hyperplasia. They were greater than 72 g in combined weight and were occupied by numerous yellow nodular/subnodular lesions. Histologically, hyperplastic lesions were composed of small compact, small clear, and usual clear cells. All of these three elements contained cells positive for PCNA but were negative for HLA-DR alpha. Small compact cells often showed positive staining for vimentin. Small cells showed underdeveloped organelles with rare nuclear grooving and were poor in lipochrome. The results are consistent with the view that AIMAH is primarily a nodular hyperplasia of the upper zona fasciculata and that it is a distinct subtype of Cushing's syndrome. Image analyses may play a major role on preoperative diagnosis of AIMAH. Bilateral adrenalectomy is the treatment of choice.

Adrenal Cortex↗
PubMed1999

Aromatase overexpression and breast hyperplasia, an in vivo model--continued overexpression of aromatase is sufficient to maintain hyperplasia without circulating estrogens, and aromatase inhibitors abrogate these preneoplastic changes in mammary glands.

To test directly the role of breast-tissue estrogen in initiation of breast cancer, we have developed the aromatase-transgenic mouse model and demonstrated for the first time that increased mammary estrogens resulting from the overexpression of aromatase in mammary glands lead to the induction of various preneoplastic and neoplastic changes that are similar to early breast cancer. Continued overexpression of aromatase that leads to increased breast-tissue estrogen contributes to a number of epigenetic changes in mammary tissue such as alteration in the regulation of genes involved in apoptosis, activation of genes involved in cell cycle and cell proliferation, and activation of a number of growth factors. Our current studies show aromatase overexpression is sufficient to induce and maintain early preneoplastic and neoplastic changes in female mice without circulating ovarian estrogen. Preneoplastic and neoplastic changes induced in mammary glands as a result of aromatase overexpression can be completely abrogated with the administration of the aromatase inhibitor, letrozole. Consistent with complete reduction in hyperplasia, we have also seen downregulation of estrogen receptor and a decrease in cell proliferation markers, suggesting aromatase-induced hyperplasia can be treated with aromatase inhibitors. Our studies demonstrate that aromatase overexpression alone, without circulating estrogen, is responsible for the induction of breast hyperplasia and these changes can be abrogated using aromatase inhibitors.

Animals↗
PubMed1987

Regression of simple hyperplasia and papillomas and persistence of basal cell hyperplasia in the forestomach of F344 rats treated with butylated hydroxyanisole.

The reversibility of forestomach lesions induced in rats by butylated hydroxyanisole (BHA) was examined. F344 rats were given a 2% BHA diet for 24, 48, or 72 wk followed by a basal diet for the remainder of the 96-wk experiment. Two other groups of rats were given a 2% BHA diet or basal diet alone for 96 wk. The forestomach lesions at wk 24, 48, 72, or 96 were compared histopathologically. The results showed that exophytic epithelial proliferation (simple hyperplasia or papilloma) induced by BHA was reversible, while endophytic proliferation of basal cells (basal cell hyperplasia) persisted after withdrawal of BHA administration. This suggests that simple hyperplasia and papilloma of the forestomach induced by BHA are not autonomous and need continuous feeding of BHA to develop further.

Animals↗
PubMed1996

[Hepatic adenoma and focal nodular hyperplasia: difficult differential diagnosis. Presentation of a case of focal nodular hyperplasia].

Hepatic adenoma and focal nodular hyperplasia are unfrequent benign lesions of the liver with individual histologic characteristics, but not always clinically distinguishable. The main difference is the intratumoral or intraperitoneal bleeding risk (high in adenoma and virtually zero in focal nodular hyperplasia). Surgery is the elective treatment for the first, while a more conservative attitude is allowed for the second. We present the case of a woman with an hepatic mass that clinically and radiologically seemed to be an adenoma. An atypical hepatectomy was done uneventfully. The examination of the specimen showed shaw focal nodular hyperplasia. We review the diagnostic and therapeutic controversy between these entities, because only the histologic examination of the entire surgical specimen could demonstrate the real nature of the lesion.

Adenoma↗
PubMed2000

Serenoa repens for benign prostatic hyperplasia.

OBJECTIVES: This systematic review aimed to assess the effects of Serenoa repens in the treatment of Benign Prostatic Hyperplasia (BPH). SEARCH STRATEGY: Trials were searched in computerized general and specialized databases (MEDLINE, EMBASE, Cochrane Library, Phytodok), by checking bibliographies, and by contacting manufacturers and researchers. SELECTION CRITERIA: Trials were eligible if they (1) randomized men with BPH to receive preparations of Serenoa repens (alone or in combination) in comparison with placebo or other BPH medications, and (2) included clinical outcomes such as urologic symptom scales, symptoms, or urodynamic measurements. Eligibility was assessed by at least two independent observers. DATA COLLECTION AND ANALYSIS: Information on patients, interventions, and outcomes was extracted by at least two independent reviewers using a standard form. The main outcome measure for comparing the effectiveness of Serenoa repens with placebo or other BPH medications was the change in urologic symptom scale scores. Secondary outcomes included changes in nocturia and urodynamic measures. The main outcome measure for side effects was the number of men reporting side effects. MAIN RESULTS: 2939 men from18 randomized trials lasting 4 to 48 weeks were assessed. 16 trials were double-blinded and treatment allocation concealment was adequate in 9 studies. Compared with placebo, Serenoa repens improved urinary symptom scores, symptoms, and urinary flow measures. The weighted mean difference (WMD) for the urinary symptom score was -1.41 points (scale range 0-19), (95%CI = -2.52, -0.30, n = 1 study) and the risk ratio (RR) for self rated improvement was 1.75 (95%CI = 1.21, 2.54, n = 6 studies). The WMD for nocturia was -0.76 times per evening (95%CI = -1.22, -0.32; n = 10 studies). The WMD for peak urine flow was 1.93 ml/sec (95%CI = 0.72, 3.14, n = 8 studies). Compared with finasteride, Serenoa repens produced similar improvements in urinary symptom scores (WMD = 0.37 IPSS points (scale range 0-35), 95%CI = -0.45, 1.19, n = 2 studies) and peak urine flow (WMD = -0.74 ml/sec, 95%CI = -1.66, 0.18, n = 2 studies). Adverse effects due to Serenoa repens were mild and infrequent. Withdrawal rates in men assigned to placebo, Serenoa repens or finasteride were 7%, 9%, and 11%, respectively. REVIEWER'S CONCLUSIONS: The evidence suggests that Serenoa repens improves urologic symptoms and flow measures compared with placebo. Serenoa repens produced similar improvement in urinary symptoms and flow compared to finasteride and is associated with fewer adverse treatment events. The long term effectiveness, safety and ability to prevent BPH complications are not known.

Androgen Antagonists↗
PubMed1988

Myoid cell differentiation in true thymic hyperplasia and lymphoid hyperplasia.

Four cases of thymic hyperplasia (TH) and/or lymphoid hyperplasia (LH) were investigated immunohistochemically for evidence of myoid cell (MC) and epithelial cell (EC) differentiation using antibodies to myoglobin, desmin, and cytokeratin. Although MCs were identified in all the cases, the most impressive perifollicular proliferation of ECs and MCs was seen in the hyperthyroid patient with TH/LH, suggesting that these cells have a role in immune function. The unusual combination of LH and TH in this patient demonstrates that exceptional cases can show overlapping features of what are otherwise considered to be separate thymic lesions. The observations that MCs occur in close proximity to ECs and ECs are depleted along with MCs in myasthenia gravis provide strong evidence supporting closely related histogeneses for ECs and MCs within the thymus.

Adolescent↗
PubMed1994

Expression of p53 protein in benign epithelial hyperplasia, atypical ductal hyperplasia, non-invasive and invasive mammary carcinoma: an immunohistochemical study.

To clarify whether p53 protein expression is involved in multistep carcinogenesis or the progression of mammary ductal carcinoma, we investigated p53 protein expression in 83 invasive ductal carcinomas (IDC), 10 IDC with a predominant intraductal component, 13 non-invasive ductal carcinoma (NIDC), 16 atypical ductal hyperplasia (ADH) and 39 benign epithelial hyperplasia (EH), using immunohistochemistry. Expression of p53 protein was detected in 24 (28.9%) cases of IDC, 5 (50%) cases of IDC with a predominant intraductal component and 1 (7.6%) case of NIDC. No expression was observed in either ADH or EH. In IDC, including cases with a predominant intraductal component, p53 protein expression was associated with a higher histological grade (P < 0.0001) or mitotic index (P < 0.0005). Although overexpression of c-erbB-2 protein has also shown a similar association with these prognostic indicators, expression of p53 protein correlated regardless of the status of c-erbB-2 overexpression. Completely coordinated expression of p53 protein was seen in both intraductal and invasive components. The intraductal component in IDC including cases with a predominant intraductal component which expresses p53 protein had significantly higher histological grade (P < 0.0005) or more comedo-subtypes (P < 0.0001). These results suggested that p53 protein expression occurs at a stage of NIDC with high histological grade or in comedo-subtypes. Its expression is maintained throughout invasion.

Breast↗
PubMed1993

Adenomatous hyperplasia of the liver resembling focal nodular hyperplasia in patients with chronic liver disease.

Two nodules of hepatic adenomatous hyperplasia (AH) resembling focal nodular hyperplasia were found in two patients with cirrhosis or chronic active hepatitis. Imaging techniques suggested that the nodules were hepatocellular carcinoma. Pathological examination showed that the nodules (approximately 1.0 cm in diameter) were clearly demarcated from the surrounding liver tissue, and contained foci of scar-like fibrosis in the centre of the nodules. Microscopically, they contained portal tracts and fulfilled the criteria of AH. A large number of arteries were present in the central scar-like fibrosis as well as in the parenchyma of the nodules. There were foci of mildly atypical hepatocytes in one nodule but no cellular atypia in the other. Morphometric analysis showed that the cumulative luminal area of arteries per unit area was much greater in the nodules than in the extranodular liver tissues, while the cumulative luminal area of portal veins per unit area was much less in the nodules than in the extranodular liver tissues. Although the pathogenesis is unclear, these nodules might have developed through localized vascular changes associated with chronic liver disease, may have arisen from pre-existing arterial malformation, or may represent the early stages of angiogenesis in hepatocarcinogenesis.

Adenoma↗
PubMed1987

Thymic hyperplasia. II. Lymphofollicular hyperplasia of the thymus. An immunohistologic study.

The so-called lymphofollicular hyperplasia, which is caused by the occurrence of hyperplastic lymph follicles within the organ, is constantly associated with autoimmune diseases (e.g., myasthenia gravis) and in rare instances with malignant tumors. The architecture of lymphofollicular hyperplasia was studied immunohistochemically using antibodies against epithelial, vascular, lymphocytic, and histiocytic antigens. There is evidence, that the configuration, microtopography, cellular composition, and immunohistological findings of the lymph follicles with germinal centers in the myasthenic thymus are essentially the same as in those occurring in lymph nodes and in other lymphatic tissue. Furthermore it could be shown that the follicles originate in the interlobular septal space and displace the thymic parenchyma by extension.

Adolescent↗