Immunohistological studies on clinically silent pituitary adenomas

Clinically inactive adenomas represent 30.7% of all pituitary tumors in our surgical collection of 616 cases. Ninety-six tumors were studied immunohistologically with many antibodies for their hormone content. Morphological classification of these adenomas reveals oncocytic adenomas in 42 cases (44%), small cell chromophobe adenomas in 33 (34%), large cell chromophobe adenomas in 14 cases (15%), undifferentiated mucoid cell adenomas in 4 cases (4%) and undifferentiated acidophil adenomas in 3 cases (3%). Immunohistological studies performed with the six pituitary hormones GH, prolactin, ACTH, TSH, LH and FSH and additionally with α-subunit demonstrated nearly all possible combinations of hormones in adenoma cells. The most frequently occurring (29%) was LH (in 3% of adenomas alone); α-subunit followed in frequency (24%), with FSH present in 21%. Combinations of 2 hormones were detected in 16%, of 3 in 13% and of more than 3 hormones in 2%. All 6 hormones and α-subunit were negative in 48% of adenomas. It must be concluded 1) that many clinically silent adenomas are LH- or FSH- or α:-subunit-positive and therefore probably originate from gonadotropic cells, and 2) that clinically silent adenomas of acidophil cell type or mucoid cell type are rare. Although many of these adenomas apparently do not secrete the hormone which they immunohistologically contain, determining the plasma levels of the gonadotropins, and especially the α-subunit in clinical studies, may obtain a suitable and helpful clinical marker in the diagnosis of “endocrine inactive” adenomas, and especially of their recurrences.     

Simultaneous production of the alpha-subunit of glycoprotein hormones and other hormones in pituitary adenomas

The immunohistological classification of 97 pituitary adenomas revealed in 34 cases alpha-subunit (a-su) positive cells in the tumor tissue. In 15 cases a-su was the only hormone found, in 11 cases the beta-subunits of the glycoprotein hormones could also be detected (10 cases with LH/FSH and 1 case with TSH). In 8 cases a-su was found simultaneously together with other hormones of the pituitary (ACTH and a-su in 1 case, GH and a-su in 4 cases, prolactin and a-su in 2 cases, prolactin, GH and a-su in 1 case). A-su could be demonstrated to be partly simultaneously produced together with these hormones in identical cells and secretory granules. Next to prolactin, the a-su was the second most frequently occurring hormone that could be detected immunohistologically in our material.     

Immunohistological determination of beta-endorphin in chromophobe, clinically hormone-nonproducing hypophyseal adenomas

Pituitary adenomas are usually classified according to the nature of their proper hormonal production. Silent adenomas of the pituitary are tumors without clinical and biochemical evidence of overproduction of any known adenohypophyseal hormones. The proportion of such seemingly nonfunctioning tumors is 20 to 30%. Silent corticotropic adenomas are able to synthesize some normal or abnormal sequences of proopiomelanocortin precursor without any signs of hypercorticism. These tumors were divided into basophilic adenomas with strong periodic acid-Schiff (PAS) positivity and chromophobic adenomas with moderate or no PAS positivity. All of our cases were chromophobic adenomas. Two of the cases were positive for beta-endorphin by immunofluorescence. ACTH immunoreactivity was not present in the cells. Electron microscopic study of the adenoma cells showed small secretory granules with a halo. The diameter of these granules varied from 50 to 250 nm. Automated morphometric and densitometric investigations of silent corticotropic adenomas and adenomas from patients with Cushing's disease gave different karyometric results. The most important practical problem arising from the present investigation was the high frequency of recurrence of silent corticotropic tumors.     

胃肠激素对胃肠动力的影响

胃肠激素与其他成分如神经递质、细胞因子等互相作用、相互调节,维持机体正常生理功能。胃肠激素与胃肠运动密切相关,同时也受神经内分泌免疫网络调控,由此本文综述其在神经内分泌网络中的特殊作用及其对胃肠动力方面的影响。     

幽门螺杆菌相关性十二指肠溃疡与胃肠激素的关系

目的探讨幽门螺杆菌(Hp)相关性十二指肠溃疡(DU)患者Hp根除前后胃粘膜及血中促胃液素(Gas)和生长抑素(SS)含量变化的意义。方法采用放射免疫分析法测定Hp相关性DU患者42例Hp根除前后及正常对照者20例胃粘膜及血中Gas和SS含量。结果Hp相关性DU的患者胃粘膜及血中Gas的含量明显高于Hp阴性患者(粘膜:ng/g,226±65vs380±98;血清:ng/L,107±33vs50±8),而Hp根除后Gas含量则明显下降,Hp阳性者SS的含量低于Hp阴性患者(粘膜:ng/L,11±2 vs 42±8;血浆:ng/L,5.6±1.2vs10.2±2.3),Hp根除后SS含量显著升高,Hp感染时胃粘膜炎细胞浸润程度对Gas和SS的含量亦有一定影响。结论Gas和SS与Hp相关性DU密切相关,是参与DU发病的重要因素之一。     

An intelligent system for automatic detection of gastrointestinal adenomas in video endoscopy

Today 95% of all gastrointestinal carcinomas are believed to arise from adenomas. The early detection of adenomas could prevent their evolution to cancer. A novel system for the support of the detection of adenomas in gastrointestinal video endoscopy is presented. Unlike other systems, it accepts standard low-resolution video input thus requiring less computational resources and facilitating both portability and the potential to be used in telemedicine applications. It combines intelligent processing techniques of SVMs and color-texture analysis methodologies into a sound pattern recognition framework. Concerning the system's accuracy this was measured using ROC analysis and found to exceed 94%.     

The role of hypothalamic hormones in the pathogenesis of pituitary adenomas

There is evidence that hypothalamic hormones can regulate hormone secretion by pituitary adenomas. Hormone release by adenomas can be stimulated by hypothalamic releasing peptides; several hypothalamic inhibitory hormones or their analogues are used in the therapy of pituitary tumors to suppress hormone secretion and, in some cases, to reduce tumor size. A role for hypothalamic hormones in the development and growth of pituitary tumors has also been suggested by the association of pituitary adenomas with tumors producing hypothalamic hormones. In particular, tumors producing growth hormone-releasing hormone (GRH) or corticotropin-releasing hormone (CRH) have been associated with hyperplasia of their target adenohypophysial cells; a few have had pituitary neoplasms. Investigations have shown that some adenohypophysial cells respond to sustained stimulation by hypothalamic peptides with cell proliferation, however, it was not proven that the sustained stimulation resulted in the development of tumors. Recently, an animal model of disease was provided by mice transgenic for GRH. At 8 months of age, the mice developed pituitary mammosomatotroph hyperplasia; mice older than 12 months developed pituitary mammosomatotroph adenoma. It is suggested that continued hormonal stimulation plays a role in tumorigenesis, probably by promotion of cell replication.     

Immunohistological studies in five patients with unknown primary carcinomas and poorly differentiated neoplasms

In the evaluation of five patients with unknown primary carcinomas or poorly differentiated neoplasms, the most critical step was to obtain an accurate histological diagnosis upon which to base therapeutic options and prognosis. This required a thorough pathological examination which included histochemical and immunohistological staining of a properly prepared biopsy specimen of ample size. Two cases of lymphoma, two of carcinoma, and one of melanoma are presented in which the correct pathological diagnosis was made with immunohistological techniques permitting the institution of appropriate therapy. The value of a simple antibody panel employed with properly prepared tissue is clearly demonstrated by these cases.     

Plurihormonal pituitary adenomas: immunostaining of all pituitary hormones is mandatory for correct classification

AIMS: We studied the clinicopathological characteristics of plurihormonal pituitary adenomas. METHODS AND RESULTS: The study material included 167 plurihormonal adenomas, which consisted of 31% of the surgically removed pituitary adenomas that we collected during a 12-year period. The mean age of patients with plurihormonal adenoma was 45.7 years (range 13-75 years). There were 86 men and 81 women. All tumours were fully classified by immunohistochemical staining for seven pituitary hormones or subunits. Thirty immunohistochemical subtypes of plurihormonal adenomas were recognized. Hormonal symptoms were present in 70% of patients, while serum hormonal levels were increased in 89% of patients. Most patients had symptoms related to only one of the hormones and only 7% of patients had symptoms related to two hormones. The most common hormonal symptom was acromegaly (50%); symptoms related to hyperprolactinaemia ranked second (20%). Double immunostaining of all the possible combinations of the hormones was performed in 30 selected tumours, and they all showed mixtures of hormones in individual adenoma cells in any hormonal combinations studied. The latter finding supported the view that plurihormonal adenomas are monomorphous adenomas. CONCLUSIONS: Plurihormonal adenomas are common pituitary adenomas. Immunohistochemical staining of all pituitary hormones is mandatory for correct classification.     

Immunohistological studies of skin biopsies from patients with lepromatous leprosy

Forty-six skin biopsies from lepromatous leprosy patients were examined for immunoglobulin and complement deposits as well as mycobacterial antigens. Rabbit anti-human immunoglobulin, rabbit anti-human C3, and rabbit anti-Mycobacterium bovis (BCG) were used as the primary antigen-detecting antibodies in a peroxidase antiperoxidase technique. Of the 26 biopsies from active erythema nodosum leprosum lesions, 6 were positive for immunoglobulin or complement deposits. These deposits were found in the dermoepidermal junction, within the foamy cells, and, in one patient, around a blood vessel. Five of twenty patients with lepromatous leprosy without erythema nodosum leprosum showed similar deposits in the dermoepidermal junction and within foamy cells. None of these patients had these deposits around blood vessels. Mycobacterial antigens were seen in all biopsies studied. The presence of acute inflammatory infiltrates did not correlate with the presence or absence of immunoglobulin or complement deposits. It is felt that immunoglobulin or complement deposits are not a constant feature of early erythema nodosum leprosum lesions and that these deposits may be secondary rather than primary in these lesions.     

Breast cancer: hormones and other risk factors

In North America and Northern Europe, breast cancer incidence rates begin increasing in the early reproductive years and continue climbing into the late seventies, whereas rates plateau after menopause in japan and less developed countries. Female gender, age and country of birth are the strongest determinants of disease risk. Family history and mutations in the BRCA1 and BRCA2 genes are important correlates of lifetime risk. Genetic polymorphisms associated with estrogen synthesis and metabolism are currently under study. Atypical hyperplasia and molecular alterations in benign breast lesions appear to be involved in the pathogenesis of invasive carcinoma. In postmenopausal women, increased breast density on mammograms increases risk. Bone density and breast cancer are associated, presumably through the mechanism of endogenous estrogen levels. Serum estrogen levels are higher in breast cancer cases than controls. Many established risk factors for breast cancer may function through and endocrine mechanism. Current use of oral contraceptives and prolonged, current or recent use of hormone replacement therapy moderately increase risk. Tamoxifen and possibly other selective estrogen receptor modulators reduce breast cancer risk in high risk women. Relationships between various dietary micro and macronutrients and breast cancer have been suggested but require evaluation in clinical trials. Whereas alcohol consumption is associated with increased risk, most environmental factors, including polychlorinated compounds and electromagnetic fields, are not. Conclusion: Breast cancer etiology is becoming clearer through the study of molecular alterations in germline and somatic cell genes, and the interaction of these genes with steroid hormones and relevant growth factors. This knowledge should be useful for breast cancer prevention.     

DNA measurement,proliferation markers,and other factors in pituitary adenomas

To assess the proliferative activity of pituitary adenomas, 36 surgically removed adenomas were studied by light microscopical parameters; mitotic count; expression of PCNA, Ki-67, cathepsin D, and EGF; and image cytometry. Three adenomas (9%) showed high, 11 (34%) medium, 17 (53%) moderate, and 1 (3%) low structural differentiation. In 10 adenomas (31%), no mitosis was observed. The average was 2.4 mitoses/100 HPF; the highest count was 7.1 mitoses/100 HPF. Eleven adenomas (33.3%) were PCNA-negative; in 20 adenomas (60.6%), between 0.05 and 3.9, and in 2 adenomas (6.0%), between 10.5 and 16.4 PCNA-positive nuclei were observed. Only a recurrent null-cell adenoma (9%) was Ki-67-negative. Three adenomas (9.1%) were EGF-negative, 28 (84.8%) showed up to 10% positive cells, and 2 (6.1 %) showed between 10 and 30% positive cells; 19 adenomas (68%) were cathepsin D-negative, including all endocrine-inactive adenomas. Half the adenomas had an euploid DMA stem line. Endocrine-inactive adenomas displayed a higher rate of euploid DNA stem lines than endocrine-active adenomas. The S-phase fraction varied between 2.97 and 28%, with a mean value of 14.4%. Half the adenomas showed an S-phase fraction of 11.65% or lower.     

Expression of glycoprotein hormones and intracytoplasmic distribution of cytokeratin in growth hormone-producing pituitary adenomas.

Sixteen growth hormone (GH)-producing pituitary adenomas were studied for the expression of glycoprotein hormone subunits and cytokeratin by light microscopic immunohistochemistry. Cytokeratin immunoreactivity was demonstrated in all adenomas, but its intracytoplasmic distribution showed two distinct patterns; a prominent, dot-like pattern and a diffuse, perinuclear pattern. Seven adenomas (type 1) were exclusively composed of cells with cytokeratin in a dot-like pattern, whereas 9 adenomas (type 2) comprised of cells with cytokeratin of perinuclear distribution. The expression of alpha-subunit of glycoprotein hormone was significantly different between the two types of adenomas; 8 of 9 adenomas of type 2 contained many alpha-subunit immunoreactive cells but none of type 1 adenomas showed any immunoreactivity. Only a small number of adenoma cells were positive for beta-subunit of thyrotropin stimulating hormone in 3 adenomas of type 2. beta-subunits of follicle stimulation hormone and luteinizing hormone were negative in all adenomas. These findings suggest that the expression of glycoprotein hormone subunits in GH-producing adenomas may be closely linked to their types distinguishable by the cytokeratin distribution pattern.     

Immunohistological studies of lymphoproliferative lesions in a fatal case of Epstein-Barr virus infection.

A fatal case of infectious mononucleosis occurred in a young adult. Abnormal serological features were noted in his mother, although there was no other family history suggesting an inherited defect of immune response to Epstein-Barr virus (EBV). The cellular infiltrate observed in tissues obtained at necropsy was analysed with a range of specific monoclonal and polyclonal antibodies. Polyclonal plasmacytoid B cell proliferation had occurred in many tissues. These cells were positive for EBV nuclear antigen, but viral particles were not seen on ultrastructural examination, and the virus was not isolated, suggesting a non-permissive infection.