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A 44-year-old male suffered from an inactive pituitary adenoma measuring 20mm in computed tomography (CT) scan and nuclear magnetic resonance tomography (NMR). The tumor was surgically resected via the transnasal-transsphenoidal route. Surgical specimens revealed a typical, sparsely granulated adrenocorticotropic hormone (ACTH) cell adenoma, but also a granulomatous inflammation mostly in the periphery of the tumor, corresponding to a granulomatous hypophysitis. This coincidence appears to be unique and has yet not been described in the literature. Therefore, the clinical data and the pathohistologic and ultrastructural findings are presented here.

The HER-2/neu protein is overexpressed in many human carcinomas obtained from different tissues and may represent a useful target for therapy with the commercially available monoclonal antibody trastuzumab (herceptin). Novel therapeutic options are needed for metastasized adrenocortical cancer. Therefore, we studied expression of the HER-2/neu cell surface receptor protein using three different antibodies in 12 adrenal adenomas, 17 adrenocortical carcinomas and 5 pheochromocytomas. Normal adrenals (n = 5) served as controls. One adenoma showed very weak membranous immunostaining with the Dako antibody, two others showed a nonspecific cytoplasmic staining pattern. A nonspecific reaction in the cytoplasm was demonstrable in seven carcinomas with the Novocastra antibody. In all pheochromocytomas, a granular intracytoplasmic and, rarely, slightly membranous immunostaining with the Dako antibody was found. From our data we conclude that specific and significant membranous immunostaining indicating strong overexpression (grade 3) of HER-2/neu protein is not present in adrenocortical tumors. The granular cytoplasmic immunostaining of the medulla may be helpful for differentiation of adrenocortical tumors from pheochromocytomas.

Null cell adenomas and oncocytomas are clinically inactive adenomas of the pituitary gland. They do not show any significant hormone content detectable by immunohistochemistry. This study aimed at demonstrating mRNAs for all main pituitary hormones in 32 null cell adenomas and 31 oncocytomas by non-isotopic in situ hybridization using digoxigenin-labeled oligonucleotide probes. The results were compared with immunohistochemical and clinical data. Immunohistochemistry (ABC method) was done with monoclonal antibodies against PRL, GH, FSH, LH, TSH, ACTH, alpha-subunit, and Ki-67 (mib-1). The signals for hormone production were detected in both adenoma types in a range from 42% for GH in oncocytomas to 78% for beta-FSH in null cell adenomas. However, these signals are apparently not effective on hormone production, as was shown by almost negative immunostaining. Owing to the simultaneous detection of at least two mRNAs in 78% of null cell adenomas and in 94% of oncocytomas, we assume that both tumor types originate from pluripotential precursor cells that are capable of producing various hormones. According to our data, it is unlikely that the signals influence the clinical behavior.

The present study was designed to investigate the incidence and immunohistochemical characteristics of pituitary tumors in the elderly. In our surgical collection of 1925 cases, we examined tumor tissue from 15 patients over 80 years of age. Pituitaries obtained at routine autopsies from 692 subjects over 80 years of age were also investigated. Of the 15 surgical cases studied, the majority of patients presented with chiasmatic syndromes, likely caused by macroadenomas. Gonadotroph adenomas were the most frequently diagnosed tumor type, followed by null-cell adenomas and oncocytomas. There is only one case with GH cell adenoma. Among 692 autopsy cases, 79 (11.4%) pituitaries were found to contain adenomas in the anterior lobe. In one pituitary, two separate adenomas were detected, hence the number of adenomas in our material was 80. All autopsy cases were microadenomas except one. The mean diameter of adenomas was 2.2 mm. ACTH cell adenomas were the most frequently diagnosed tumor type, followed by PRL cell adenomas and null cell adenomas. The occurrence of pituitary adenomas discovered after routine autopsy in the elderly was common, although these tumors were not found frequently in surgical cases over 80 years of age. Our immunohistochemical study revealed that many tumors contained one or more than one anterior pituitary hormone, although almost all pituitary adenomas were considered to be clinically inactive in surgical and autopsy cases.

Although androgen receptors have been identified in normal gonadotroph and somatotroph cells of the pituitary, immunohistochemical studies have failed to reveal these receptors in pituitary adenomas so far. Using a monoclonal antibody to androgen receptor in our series of 60 adenomas of the gonadotroph cell complex (20 FSH/LH cell adenomas, 20 null cell adenomas, 20 oncocytic adenomas), only one null cell adenoma showed strong nuclear immunostaining. All the other antibodies were completely negative. The significance of this finding in correlation with clinical data is still unclear, although it may be associated with more rapid tumor growth. In paraadenomous tissue, some normal gonadotrophs expressed the androgen receptor.

Pituitary adenoma tissue from patients with acromegaly (n = 286) was obtained by surgery and examined for folliculo-stellate cells by immunostaining for S100 protein. The number of immunostained cells varied from one adenoma to another. A hundred and ninety-eight pituitary adenomas (69%) contained S100 protein positive cells corresponding to folliculo-stellate cells (FSC): in 100 cases (35%), only few sparse FSC were found, in 43 cases (15%) FSC were scattered throughout the adenoma, and in 55 cases (19%) there was an abundance of FSC. There were no significant differences regarding sex or age of the patients. The relative amount of FSC vaired among different adenoma types. Plurihormonal adenomas showed the highest FSC density, whereas the majority of monohormonal adenomas contained only few or no FSC. Patients with pituitary adenomas containing scattered FSC had a significantly higher preoperative mean GH level than patients with pituitary adenomas not having FSC. There was a negative correlation between the FSC density in adenoma tissue and the preoperative mean PRL level. There was no correlation between the tumour size and the amount of FSC. Our data indicate no effect of the duration of symptoms on the FSC density and do not suggest a correlation between FSC density and the percentage of a certain hormone-secreting cell type.

Twenty-seven plurihormonal and 21 growth hormone- prolactin- (GH- PRL-) mixed cell adenomas obtained from patients with acromegaly undergoing transnasal-transsphenoidal surgery were investigated immunohistochemically for expression of Epidermal Growth Factor (EGF), Transforming Growth Factor alpha (TGF alpha), Insulin-like Growth Factor-1 (IGF-1), Estrogen Receptor-Related Protein (ERRP), Multidrug Resistance Marker (MDRM), Protein Kinase C (PKC), Gs alpha,. Cathepsin D and p53. Five plurihormonal adenomas grew invasively. The panel of markers used in this study represents a selection of functional and proliferative markers thought to be associated with the function and development of pituitary adenomas. Our results imply that the growth factors (EGF, TGF alpha, IGF-1), the cell signalling protein Gs alpha and the MDRM are expressed by both types of pituitary adenomas in a similar pattern. Non-invasive GH-PRL-mixed cell adenomas showed an increased expression of IGF-1, TGF alpha and MDRM compared to non-invasive plurihormonal adenomas. No factor was found which would reliably distinguish between invasive and non-invasive adenomas. We failed to confirm the findings of others that p53 and cathepsin D might be indicators of tumor aggressiveness. A participation of ERRP and PKC in the development of bi- and plurihormonal adenomas with acromegaly appears unlikely, as the immunostains were all negative.

This report describes the clinico-pathological features of myofibroblastic tumors of the breast in six patients. Four women and one man presented with a benign myofibroblastoma. The sixth patient was a woman with myofibrosarcoma. All myofibroblastomas were composed of a fascicular arrangement of spindle cells embedded in dense bundles of collagen. Tumors differed with respect to their proportion of neoplastic cells and collagenous stroma as well as cellular pleomorphism. Based on this variation, the tumors could be subclassified as classic, collagenized, epithelioid and cellular myofibroblastoma. Immunohistological staining confirmed myofibroblastic differentiation by strong expression of either desmin or smooth muscle actin with coexpression of vimentin. In addition, numerous cells reacted with antibodies to CD68. Proliferative activity was rather low in the myofibroblastoma with an average of 0-2 mitotic figures per 10 HPF. DNA cytometric analysis was performed in two cases and showed diploid stem lines with minor S-phase fractions (1% and 3%). In the myofibrosarcoma, cells contained pleomorphic nuclei with some giant cells and numerous mitotic figures (6-7/10 HPF) and had infiltrating margins that were apparent even grossly. Immunohistochemically, tumor cells strongly expressed vimentin, smooth muscle actin and fibronectin. Ultrastructurally, neoplastic cells met the criteria of myofibroblasts, i.e. contained abundant intermediate filaments and myofilament bundles with focal densities as well as fibronexus junctions. DNA cytometric analysis exhibited again a diploid stemline but marked proliferative activity was present as indicated by an S-phase fraction of 20%. In conclusion, in benign myofibroblastoma there may be some cellular pleomorphism but mitotic activity is always low. The malignant counterpart, myofibrosarcoma, is characterized by marked cellular pleomorphism, infiltrating margins and high mitotic rate.

Previous studies have shown that corpora amylacea (CA) in certain organs, including the prostate, lung and uterus, are composed of amyloid. This observation raises the question of whether these amyloid deposits share a common origin or demonstrate the diversity which characterizes other amyloid syndromes. Sections of the lung, prostate and uterus from 110 consecutive autopsies of individuals over 84 years of age were studied initially using H & E and Congo red staining. CA were present in 54 cases (49%) with the prostate affected in 23 cases, the lung in 19 cases and the uterus in 15 cases. Immunohistochemistry with a panel of antibodies directed against the major amyloid fibril proteins, i.e. AA, A beta 2M, A lambda, A kappa and ATTR, yielded strong immunoreactivity of prostatic and pulmonary CA with anti-A beta 2M. Immunostaining with an antibody against cytokeratin (KL1) gave a weak reaction in a single case of prostatic CA, indicating that it is unlikely that these CA derive from cytoskeletal remnants of shedded epithelial cells. The uterine CA were not stained by any of the antibodies, suggesting that they have a different origin than prostatic and pulmonary CA. The influence of the local calcium concentration and niduses on the pathogenesis of CA is discussed.

Gliomatosis peritonei (GP) is the metastatic implantation of glial cells within the peritoneal cavity of patients with ovarian teratomas. The case of a young woman is presented, who initially developed a mature teratoma in the left ovary that was surgically removed. Nine years later a mature teratoma in the right ovary was excised, upon which GP was found in the greater omentum. To identify the cellular composition of the ovarian teratoma and of the omental implants, immunostainings were performed using antibodies against glial and neuronal antigens as well as against determinants of hematopoietic cells. In the teratoma the neuroectodermal part was strongly HNK-1-positive and contained GFAP- and vimentin-positive astrocytes and some NSE-positive neuron-like cells. In addition, neuroectodermal tissue was infiltrated by numerous CD68-positive macrophages/histiocytes and CD20-positive B lymphocytes. The omental nodules consisted of astrocytes, which expressed GFAP, vimentin and desmin. The implants also contained macrophages/histiocytes, which exhibited morphologic features reminiscent of microglial cells. In GP, macrophages might release glia-promoting trophic factors, which could allow the neural component of ovarian teratoma to implant in the peritoneal cavity and survive there for many years. Macrophage-derived factors might induce astroglial differentiation, which could explain why the peritoneal implants are mostly mature even when they originate from immature teratomas.

The prevalence of gastrointestinal amyloid was determined in 110 consecutive autopsy patients aged 85 years and older. Paraffin sections from the esophagus, stomach, small intestine, colon and rectum were stained with Congo red and inspected in polarized light. Amyloid was found in 38 patients (36%). Four patients had generalized amyloidosis and the remaining 34 revealed more localized varieties of amyloid. Immunohistochemical classification with a panel of antisera directed against five major amyloid fibril proteins displayed at least four different types of amyloid. Twenty cases exhibited amyloid of transthyretin origin, five cases were of lambda light chain origin and one case was of amyloid A-type. Thus far, unclassifiable amyloid deposits were found in 18 cases, 16 of which were strictly localized in subserosal veins. This consecutive autopsy series was compared with 98 randomly-selected bioptical gastrointestinal tissues with amyloid according to distribution pattern, sex, frequency of the various types of amyloid and associated diseases.

In a continuous series (1979-1989) of autopsies (n = 4,077) acute venous thromboses or pulmonary embolisms were found in 966 cases (23.7%). Fresh pulmonary embolisms were present in 758 cases (18.6%) and thromboses without embolisms were demonstrated in 208 (5.1%) autopsies. Fulminant fatal embolism leading to death was found in 598 cases (14.6%). In some cases with embolism (n = 56; 7.4%) a vein thrombosis was not demonstrable. In 62.1% of embolisms thromboses originated from pelvic or femoral veins and in 22.8% from calf veins. A comparison of the series of thromboses with a control group free of thromboses showed significant (p < 0.05) differences: a) thromboses are more frequent in females; b) patient's weight was higher in group with thromboses (59.4 kg versus 56.7 kg); c) the period of rest in hospital was longer in group with thrombosis (19.0 days versus 101.4 days); d) malignancies were more frequent in study group (54.5% versus 47.1%); e) hematocrit was higher in group with thrombosis (39.1% versus 37.5%); f) cases treated with heparin (15,000 IE sc daily) and patients with hepatic insufficiency are overrepresented in control group.

We studied the effects of the long-acting somatostatin analogue octreotide (SMS 201-995, Sandoz, Basel, Switzerland) on the morphology of pituitary adenomas in acromegaly. Of the 29 adenomas examined by light microscopy, 16 had been treated pre-operatively with octreotide. The treated adenomas were compared with the untreated adenomas. 14 adenomas were also studied by electron microscopy. In 23 cases we performed in-situ-hybridization for GH-mRNA. Under light microscopy, we found a decrease in amyloid deposits and a higher amount of cell necroses and fibroses after treatment, mainly in the tumors with shrinkage. Tumor shrinkage was diagnosed when the maximal diameter of the adenoma decreased for at least 1/3 during octreotide treatment in NMR examination. Immunohistochemical examinations showed that treated adenomas, especially those with tumor shrinkage, possessed more GH immunoreactive cells, and after in-situ-hybridization we found a higher content of GH-mRNA. On the ultrastructural level, rough endoplasmic reticulum appeared to be increased in treated adenomas. The increase of GH-mRNA and of rough endoplasmic reticulum suggests the likelihood of an increased secretory activity due to a rebound effect after short-term pre-operative omission of octreotide. Other findings are discussed.

For the assessment of the anatomical distribution of cerebral amyloid angiopathy (CAA) as well as that of amyloid plaques (AP), 955 post-mortem brain specimens from 653 patients (aged 14 to 95 years) were made available from a general hospital. Using histological and immunohistochemical techniques, we demonstrated amyloid angiopathy chiefly in the occipital, parietal and temporal regions. Senile plaques were mostly found in parietal, temporal and occipital areas. In our cases, neurofibrillary tangles were rarely prominent in the regions examined. There was often a significant difference in the frequency of amyloid angiopathy and of plaques in distinct areas between men and women. Congophilic angiopathy was associated with senile plaques in 82.3%, and neurofibrillary tangles with plaques in 76.9%. In comparison, the correlation of amyloid plaques with CAA (32.5%) and of plaques with neurofibrillary tangles (11.5%) was less pronounced. There was a strong association of cerebral vascular amyloid with age in both sexes, it was more pronounced in women than in men. Unexpectedly, CAA showed a decrease in frequency in men in the 7th and 8th decade of life. In addition, there was a positive correlation between the amount of CAA and spontaneous hemorrhages, but no correlation with ischemic encephalopathy. Immunohistochemistry showed that cerebral amyloid was neither amyloid of the AA- nor of the ATTR-(Antitransthyretin-, formerly anti-AF)-type. An antibody to the beta-protein (anti-A beta) showed cerebral vascular deposits to be congruent with the Congo red method, whereas senile plaques stained weakly and neurofibrillary tangles could not be stained at all with these antibodies.

A collection of 13 tumors causing an ectopic Cushing's syndrome was composed of four bronchial carcinoids, one small cell carcinoma of the bronchus, one thymic carcinoid, two islet cell tumors of the pancreas, one pheochromocytoma, two medullary carcinomas of the thyroid, one prostatic cancer and one intrasellar choristoma. By immunohistochemistry, ACTH in combination with CRH was found in one bronchial carcinoid and in one islet cell carcinoma. ACTH but not CRH was demonstrable in one bronchial carcinoid, in both medullary carcinomas of the thyroid, in the thymic carcinoid and in the pheochromocytoma. CRH without ACTH was present in the small cell carcinoma of the bronchus, one bronchial carcinoid, the prostatic cancer and the choristoma of the sellar region. Neither ACTH nor CRH could be found in one islet cell carcinoma. In the pituitary (n = 7) Crooke's cells were found except in one case with islet cell carcinoma which was treated with adrenostatic drugs. The pituitary besides the intrasellar choristoma harbored an ACTH cell adenoma. The pathophysiological correlations are discussed.

The frequency and the significance of the 3 main features of pituitary in Cushing's disease (ACTH secreting adenomas, ACTH cell hyperplasia, and Crooke's cells) are reported and discussed. In our most recent surgical series (1989-1990) the rate of demonstration of adenoma increased up to 96%. The frequency of paraadenomatous ACTH cell hyperplasia depends on the amount of resected tumor-free tissue. The significance of such peritumorous hyperplasia seems to be low. Crooke's cells as suppressed and transformed ACTH cells were present in each case and are a reliable indicator of a hypercortisolism.

528 biopsies from 396 pituitary adenomas were re-examined by light microscopy and checked for invasion of neighbouring tissues. The overall invasion rate was 41.9%. Highly differentiated ACTH-cell adenomas were invasive in 24.1%, undifferentiated mucoid-cell adenomas in 66.7%. The histological type of invasion was influenced by the adenoma type and by the invaded tissue. There was no obvious correlation between the adenoma type and the invaded tissue.

In a series of 40 pituitary adenomas in acromegaly all tumors showed mRNA for GH by in situ hybridization (ISH). The signals were mostly very strong and found in more than 80% of adenoma cells by using frozen sections. In paraffin sections the number of positive cells and the intensity of signals are lower. Prolactin mRNA was found in 87% of adenomas. In 27% more than 80% of cells were marked. beta-HCGmRNA (with 90% hormology for LH-mRNA) was demonstrable in very sparse cells of 25% of adenomas. Comparing ISH with immunohistology (IH) we found a correlation between signals and hormone content in 100% of adenomas for GH, in 60% for Prolactin and in 10% for Gonadotropins. In 18% Prolactin mRNA but not the hormone was demonstrable and in 5% Prolactin was immunostained but no hybridization signals were detected. In a series of 40 clinically inactive adenomas sparse cells of three tumors expressed GHmRNA and two of these contained also the hormone, whereas in one adenoma GH but not GHmRNA was demonstrable. Prolactin mRNA was found in 8 adenomas. 7 of these also contained the hormone. In two cases Prolactin but not Prolactin mRNA was present. Beta-HCG(LH)mRNA and the respective hormones were shown in very sparse cells of 6 adenomas, whereas only beta-HCG(LH)-mRNA was found in 8 cases. The significance of the findings is discussed.

The first study was undertaken for detecting hormone-receptors for estrogen and progesteron with immunohistochemical methods in frozen sections of 58 pituitary adenomas of different types. In all cases the result was negative. In the second study we tested the binding pattern for the lectins Peanut lectin (PNA), Ulex europaeus agglutinin (UEA-1) and the Concanavalin agglutinin (Con-A) in 144 pituitary adenomas of different types and in 20 post-mortem pituitaries using the two-layer indirect technique. All normal pituitaries reacted positive for all three lectins, elsewhere the binding feature for pituitary adenomas was different. Via statistical analysis, correlating lectin-bindings with clinical hyperfunction and immunohistochemical hormone content, we found an association of acromegaly and PNA and ConA and of Cushing's disease and PNA and UEA-1; furthermore of GH and UEA-1 and Con-A, of TSH and UEA-1 and of ACTH and PNA and UEA-1. Using serial sections (AB-method for demonstrating hormones and two layer indirect technique for lectin-binding) and the double-staining technique (labelled Streptavidin-Biotin-method for demonstration of hormones and the two-layer indirect technique for lectins) we found Con-A reacting with GH and PRL cells and with a part of FSH-cells, UEA-1 reacting with most of the ACTH-cells and PNA reacting with FSH-cells.

By electron microscopical morphometry (point counting method) 4 groups of adenomas were compared in order to identify the source of prolactin in hyperprolactinemia. The 4 types of adenomas were characterized by the following features: Group I: acromegaly without hyperprolactinemia (GH positive and PRL negative on the immunohistochemical level); Group II: acromegaly with hyperprolactinemia and/or galactorrhea (GH positive and PRL positive on the immunohistochemical level); Group III: adenomas with hyperprolactinemia without acromegaly (GH negative and PRL positive on the immunohistochemical level); Group IV: adenomas with hyperprolactinemia without acromegaly (GH and PRL negative on the immunohistochemical level). Morphometry was performed in order to analyse the relative amount of the following cellular structures: nuclei, nucleoli, rough endoplasmic reticulum, Golgi fields, immature secretory granules, mature secretory granules, lysosomes, mitochondria, unorganized cytoplasm, and cellular membranes. Significant differences (Student t-test, Wilcoxon test; 2 p less than 0.05) were found for the following compartments: rough endoplasmic reticulum and Golgi fields in group III had significantly larger volumes than in group IV. The volume of secretory granules of group II and group IV was larger than of group III. The volume of mitochondria of group IV was larger than in group I, and it was larger in group I and group III than in group II. Despite these differences a distinctive morphometrical pattern of the different subgroups could not be established. The quantitative data are valuable for interpretation of high or low functional activity but not for differential diagnoses. Therefore, if only the source of PRL in hyperprolactinemia has to be identified, immunocytochemistry is the best and simpler method.(ABSTRACT TRUNCATED AT 250 WORDS)

71 surgically removed pituitary adenomas with amyloid deposits were studied by light microscopical and immunohistological means. In none of the adenomas was there a predominance of amyloid deposits. There were no correlations between the extent or pattern of the deposits with either age, immunohistological hormone content or localization. Our results do not support either of the theories about the origin of amyloid--whether mesenchymal or produced by adenoma cells--in pituitary adenomas.

Pituitaries of 137 cases with Cushing's disease were microscopically and immunohistologically studied. Many alterations and parameters (sex, age, anamnesis, cortisol plasma levels, tumor size, invasiveness, localization, differentiation of adenomas, immunohistological hormone content, capillarity, recurrences, peritumorous ACTH cell hyperplasia, and Crooke's cells) were analyzed and compared. Whereas most parameters were not correlated, we found some important statistically significant correlations: Undifferentiated adenomas are more frequently invasive than differentiated ones. Invasive adenomas recur more frequently than non-invasive adenomas. Extremely laterally localized adenomas are more often invasive. Larger adenomas are more frequently invasive than micro-adenomas. ACTH cell hyperplasia are more often demonstrable in specimens from total hypophysectomies (confined to our earlier series) than from partial hypophysectomies and adenomectomies. Recurrences of adenomas are more frequent in pituitaries with periadenomous ACTH cell hyperplasia. Very rarely ACTH cell hyperplasia are the only source of ACTH hyperfunction. The more Crooke's cells are demonstrable, the longer the post-operative replacement dose of Cortisol is required. Adenomas in Cushing's disease and adenomas in Nelson's syndrome differ significantly in the following points: Adenomas in Nelson's syndrome are larger and contain more plurinuclear cells. In the ultrastructure, adenomas in Cushing's disease show more cytofilaments. Paraadenomous Crooke's cells are lacking in Nelson's syndrome.

A marker for T-lymphocytes (UCHL 1) was immunohistologically found in many folliculo-stellate cells of the normal human anterior pituitary. Another antibody for T-lymphocytes (MT 1) and a marker for B-cells were negative. The results must be critically discussed.

3 pituitary adenomas in hyperprolactinemia and 3 GH and prolactin producing tumours were analysed. The adenoma cells were prepared and held in suspension so that they could be treated with bromocriptine (10 ng and 100 ng). At different times after treatment (0.5, 60 and 90 minutes), the cells were fixed and prepared for conventional electronmicroscopy. Electron microscopic photographs were quantitatively analysed by the point counting method. The results were compared to those of an untreated control group. After bromocriptine influence, there was a decrease of the hormone secretion into the supernatant (2 of 3 prolactin producing adenomas). The prolactin secretion was unchanged in all 3 adenomas which produced prolactin and GH, but there was a decrease in the GH production in 1 of these cases. Ultrastructural morphometry revealed the following results: In prolactin producing adenomas, there was a decrease in the number of exocytoses, an increase in the volume density of lysosomes (2 cases) and an increase of the rough endoplasmic reticulum (1 case). The decrease of the "unorganized" cytoplasm was observed in all 3 cases, but was significant only in 1 case. There was a significant increase in secretory granules (1 case). In adenomas which produced prolactin and GH displayed a significant increase of the rough endoplasmic reticulum and of the granules. The outlines of the cellular membranes seemed smoother (1 case). The heterogeneous results may be interpreted as an expression of the reduced hormone secretion (secretory granules, lysosomes), some data are in accordance with the beginning of necrobiotic phenomena (rough endoplasmic reticulum). The decrease of the "unorganized" cytoplasm may be due to a shrinking process.

An 18-month old infant with Cushing's disease due to an ACTH producing pituitary tumor is presented. The case showed typical clinical and morphological sings of hypercortisolism. The infant died of pulmonary thromboembolism after transsphenoidal partial adenomectomy. The adrenals were diffusely hyperplastic. The pituitary adenoma was classified as an undifferentiated mucoid cell adenoma with sparse granulation by light microscopy. Immunoenzymatic studies demonstrated ACTH not only in granulated adenoma cells. Ultrastructurally the cells were only differentiated as typical ACTH cells or so-called follicular cells in small areas. Most of them were undifferentiated, showing pleomorphism of the relatively sparse organelles. In-vitro experiments using suspensions of adenoma cells showed a distinct enhancement of ACTH secretion after arginine-vasopressin and a further decrease ultrastructurally in the number of secretory granules. No effect of ACTH levels and no alterations of the ultrastructure were observed after cortisol. The case is representative of typical hypothalamic-hypophyseal Cushing's disease with an undifferentiated pituitary adenoma secreting ACTH in part autonomously. This constellation of Cushing's syndrome is extremely rare at the age of one year. Our case is the second one reported in the literature.

19 macroprolactinomas and 1 microprolactinoma were analysed by light microscopical, immunohistological and ultrastructural as well as morphometrical methods. 8 adenomas were removed from patients who were treated preoperatively with bromocriptine and/or Lisurid for different periods. 18 of 20 adenomas were positive for PRL on the immunohistological level. One case was negative. This patient showed a good response to the pharmacological treatment. The ultrastructure of this case revealed many secretory granules. A morphometric analysis of the ultrastructure could be performed in 19 cases; 1 case had to be excluded because of large necrotic areas. The following qualitative significant alterations after the treatment could be established: Reduction of the volume density of the rough endoplasmatic reticulum; Reduction of the size of the granula diameter; Increase of the volume density of the more irregular and indented nuclei. Other alterations were as follows: Reduction of the nuclear size; Increase of the number of secretory granules and of the volume density of lysosomes. These changes were to be observed in most of those tumors which responded to the dopamine agonist treatment. The non-responding adenomas and one which was removed 6 days after having discontinued a successful preoperative medical therapy were similar to the untreated adenomas. The results display the influence of dopamine agonist on the hormone synthesis, release and degradation in PRL secreting adenoma cells.

Two highly differentiated acidophil prolactin-cell adenomas with hyperprolactinemia (group I), 8 large cell chromophobe adenomas with hyperprolactinemia (group II), and 2 small cell chromophobe adenomas (group III), one of which was combined with hyperprolactinemia, were studied immunohistologically. Morphometry was performed on the light- and electron microscopical level. The 11 active adenomas were immunohistologically positive for prolactin, the 12th adenoma with normal prolactin plasma level was negative for prolactin. Light microscopical morphometry displayed significantly more cells of smaller size in the "small cell chromophobe" adenomas, whereas the large cell chromophobe adenomas and the highly differentiated prolactin cell adenomas were not different. Ultrastructural morphometry demonstrated significant differences between highly differentiated prolactin cell adenomas (group I), and large cell chromophobe adenomas (group II). The latter contain smaller "relative volumes" of nucleoli and of secretory granules, whereas the rough endoplasmic reticulum, the Golgi fields and the nuclei were not different. Comparison of large cell chromophobe adenomas (group II), and small cell chromophobe adenomas (group III) revealed significantly larger relative volumes of nuclei and of mitochondria but smaller volumes of rough endoplasmic reticulum and of Golgi fields in the small cell chromophobe adenomas. Significant differences between the active and the inactive adenoma of small cell chromophobe type in the group III were not found. In spite of the low quantity of small cell chromophobe adenomas and of acidophil prolactin cell adenomas, our data demonstrate that there exist distinct and significant light microscopical and ultrastructural differences between the three adenoma types.(ABSTRACT TRUNCATED AT 250 WORDS)