[Multiple primary malignant tumors in an unselected autopsy sample].
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Biomedical subjects
Publications and source records attributed to W Saeger.
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This paper reports on the experiences gathered in respect of medical care during a ten-day youth camp with members of German girl guide and boy scout associations in the summer of 1988 comparising 6,000 youngsters. Large-scale tent camping of children and adolescents lasting for several days requires a costly and complicated infrastructure for self-support. A medical aid unit where patients can also be looked after on an inpatient basis if necessary, is mandatory if there are more than approximately 300 campers. There should be a doctor-participants ratio of 1:500 or 1:800 for "around-the-clock" availability of medical aid. One of the doctors in the medical team should be a surgeon or a doctor particularly skilled in minor surgery. Every doctor should have three medical assistants at his disposal. Cooperation with hospitals and practising physicians in the neighbourhood should be clarified and organised beforehand. The most frequently occurring diseases in the tent camp were injuries (36% of the patient material), infectious diseases (30%) often of a viral nature and physically conditioned noxae (sunburn, solar dermatitis, burns). About 8% of the patients had to be treated on an inpatient basis in the medical camp unit. Severe lesions or injuries were very rare, probably mainly thanks to the disciplined behaviour of the participants in the camp.
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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.
Light microscopical morphometry was performed on 10 adenomas with oncocytic parts (26%-50% oncocytes, group I), on 9 oncocytic adenomas with 51%-75% oncocytes (group II), and on 12 oncocytic adenomas with 76%-100% oncocytes (group III). We measured the area and circumference of nuclei and areas of cells. Furthermore, shape factors for area and circumference of nuclei and the quotients of nuclei area/cell area were calculated. Data of about 40,000 single measurements were evaluated statistically. There is a clear positive correlation of cell areas compared to the proportion of oncocytes in the respective adenoma. A gradual, steady enlargement of cells can be observed, whereas enlargement of nuclei is seen to a much less extent. Consequently the quotients of area of nuclei/area of cells become smaller with increasing oncocytic transformation, evidence that enlargement of cells takes place in favour of cytoplasm. The three adenoma groups differ significantly from each other in their average cell sizes. Regarding nuclear sizes, the difference is mainly to be seen between group II and III. Comparison of adenomas containing oncocytes with large cell and small cell chromophobe adenomas also show significant differences in sizes of cells and nuclei. Large cell chromophobe adenomas show distinctly larger nuclei, which is looked upon as a display of their endocrine activity. On the other hand, oncocytic adenomas bear comparatively small nuclei in an extended cytoplasm which may well be related to their endocrine inactivity.
Immunohistochemical analyses using antibodies against the major pituitary hormones, the alpha-subunit of glycoprotein hormones, chromogranin and synaptophysin were performed on 10 adenomas with oncocytic parts (26%-50% oncocytes, Group I), on 9 oncocytic adenomas with 51%-75% oncocytes (Group II), and on 12 oncocytic adenomas with 76%-100% oncocytes (Group III). Only 11 of the 31 investigated adenomas (35%) showed negative immunostaining for all major anterior pituitary hormones. FSH-content could be shown in 16 of 31 adenomas (52%), LH-content in 12 of 31 adenomas (39%), TSH-content in 3 of 31 adenomas (10%). Comparing all three groups of adenomas, there are no differences in the immunoreactivity to alpha-subunit (24 of 31 adenomas, 77%), chromogranin (26 of 31 adenomas, 84%), and of synaptophysin (13 of 31 adenomas, 42%). Considering the high percentage of cells of oncocytes showing alpha-subunit immunoreactivity we regard oncocytomas as originating very often from TSH-gonadotropin cell complexes of the anterior hypophysis. Alpha-subunit might become a reliable marker for oncocytomas. The finding of immunoreactivity to chromogranin in most cases confirms morphological studies that oncocytes contain some secretory granules. In most cases, the studied oncocytomas did not react to synaptophysin showing different results from other adenomas of the anterior hypophysis.
In order to clarify the mechanism by which prolactin-secreting adenomas reduce in size during treatment with dopamine agonists (DA), we studied altogether 18 chromophobe pituitary adenomas by carrying out light microscopical cell counting of necrobiotic alterations and necroses in photographs of semi-thin sections. Depending on hormonal activity and preoperative treatment of the patients 3 groups of adenomas were formed: 6 prolactin producing adenomas were treated with bromocriptine and lisuride (group 3). 8 cases remained preoperatively without medical treatment (group 2). For comparison, we studied 4 cases of clinically inactive pituitary adenomas (group 1). All adenomas were immunohistologically positive for prolactin. By classifying each tumor cell in one of four stages of necrotic alteration (stage 1: intact cell, stage 2: slightly condensed nucleus and shrunken cytoplasm, stage 3: necrotic cell with still visible nuclear membrane, stage 4: cell debris) we arrived at an index for necrobiotic alterations of the 18 adenomas. We found a significantly higher rate of cell necroses in DA-treated tumors compared with preoperatively untreated prolactinomas and inactive adenomas. Previous investigations in this field have revealed that a reduction in cell size may well cause the shrinkage of the prolactinomas after DA-therapy. The results presented in this paper indicate, however, that the role of necroses now needs to be given much closer attention as an additional factor.
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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)
In Germany, the relative frequency of pineal region tumours seems to be much higher than hitherto assumed. At the University Hospital Hamburg, from 1980-1985 17 children with pineal region tumours were encountered amongst 102 children with CNS tumours. Two-cell-type germinoma is the most frequent pineal region tumour. Cerebrospinal fluid cytology is highly successful in identifying this germ cell tumour. Surgical removal has become a reasonably safe procedure in the treatment of pineal region tumours and was successful in all 10 cases so treated. In addition, our patients with two-cell-type germinomas received craniospinal axis radiation. All children, treated by both surgical removal and craniospinal axis radiation are so far relapse-free and are functioning on a pretreatment level.
GH producing adenomas of patients with acromegaly (undifferentiated acidophil adenomas and well differentiated GH cell adenomas) were studied at the ultrastructural level and analysed morphometrically by the point counting method. They were compared with identically prepared GH cells of normal pituitaries from patients undergoing surgery for metastasizing cancer of the prostate. In the well differentiated GH cell adenomas significantly more points were counted on nucleoli, unorganized cytoplasm, rough endoplasmic reticulum, immature secretory granules, Golgi areas and on the plasma membranes, than in normal GH cells. Comparison of normal GH cells with tumour cells in undifferentiated acidophil adenomas demonstrated significantly larger volumes of nuclei, rough endoplasmic reticulum, Golgi fields, immature secretory granules and of the cell membranes, and also of nucleoli and of the mitochondria. Secretory granules and lysosomes were observed more frequently than in normal GH cells. In a comparison of both adenoma types, the well differentiated acidophil adenomas contained significantly larger volumes of the unorganized cytoplasm, secretory granules and of cell membranes, whereas more points were counted on the rough endoplasmic reticulum and on the mitochondria in undifferentiated acidophil adenomas. The differences between the normal GH cells and the GH cell in undifferentiated adenomas (mainly larger nucleoli, larger volumes of the rough endoplasmic reticulum and the lower volumes of secretory granules) indicate a higher secretory activity in the adenomas. The significant differences between the well differentiated and the undifferentiated adenomas (mainly the increased volumes of mitochondria and of the unorganized cytoplasm in the undifferentiated tumours) indicate a lower grade of differentiation and may be interpreted as signs of increased proliferation.