Biomedical subjects
Publications and source records attributed to E Horvath.
Electron microscopy of the liver of methotrexate-treated psoriatic patients revealed junctional abnormalities consisting of detachment of desmosomal plaques between hepatocytes. Mitochondria anchoring desmosomal microfilaments were frequently noted.
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Electron microscopy revealed the presence of cytoplasmic tubular aggregates in the capillary endothelium of a sparsely granulated growth hormone cell adenoma removed surgically from a 25-year-old female patient with acromegaly. To our knowledge, this is the second publication describing these structures in hypophysial growth hormone cell adenomas.
Seven cardiac myxomas (CM) were studied by light and electron microscopy (EM) and their features compared with previously reported CM. Tumor cells were enmeshed within abundant stroma composed of fine electron dense granules. These cells were present either singly or more often in closely apposed small groups. The most distinctive ultrastructural feature in all seven CM was the presence of numerous cytoplasmic filaments. Our findings did not support a distinct separation into multiple cell types that could be clearly classified since the tumor cells had combined features of smooth muscle cells and fibroblasts. There has been no agreement on the principal cell type observed in CM, which has resulted in numerous theories about their histogenesis. Although the cell of origin of CM remains elusive, we fell that CM arise from primitive mesenchymal cells with multipotential capabilities for cell differentiation. Evidence is presented supporting the fact that CM are neoplasms and not thrombi. CM rarely recur but no bona fide metastasis has been reported.
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The structural features of 26 spontaneous pituitary tumors in aging female Long-Evans rats have been investigated by different morphologic techniques including immunoperoxidase staining and electron microscopy. By light microscopy, the tumors corresponded to chromophobic-sparsely granulated acidophilic adenomas, containing numerous pigment granules and showing congestion as well as focal hemorrhages. Positive cytoplasmic staining was obtained with Herlant's erythrosin as well as with Brookes' carmoisine methods, used to detect secretory granules of prolactin cells. Immunoperoxidase technique revealed the presence of immunoreactive prolactin in the cytoplasm of many adenoma cells. Growth hormone and TSH immuno-stainings were negative. By electron microscopy, the tumors were found to consist of prolactin cells exhibiting marked variability in subcellular morphology and differing considerably from non-tumorous resting prolactin cells. A decrease in size and number of secretory granules, proliferation of rough-surfaced endoplasmic reticulum, formation of "Nebenkerne", accumulation of free ribosomes, prominence of Golgi complex and the presence of misplaced exocytosis were characteristic features of the adenoma cells and were interpreted as indicating enhanced secretory activity. Crinophagy and transformation of secretory granules into pigment deposits were striking findings in many adenomas. Since all the adenomas seemed to derive from prolactin cells and belong to the same tumor class, it is assumed that prolactin cells in female Long-Evans rats are more susceptible to oncogenic stimuli than other hypophysial cell types.
Adenohypophyses of adult male rats have been investigated by light microscopy, immunocytology and electron microscopy 30 minutes, 1, 2, 4, 6 and 24 hours following electrolyte destruction of the pituitary stalk. Light microscopy revealed massive ischemic infarction of the adenohypophysis. Immunoreactive growth hormone, prolactin, TSH, FSH and LH were demonstrated up to 24 hours after surgery in necrotic adenohypophysial cells by the immunoperoxidase technique. Fine structural abnormalities were already noticeable 30 minutes following stalk lesion. The changes rapidly progressed and within 2 hours unmistakable signs of cellular necrosis became evident. Mitochondria, especially those of growth hormone cells, seemed to be affected at an early stage, whereas alterations in rough-surfaced endoplasmic reticulum membranes developed later. Nuclear changes, formation of cytoplasmic vacuoles and disruption of cell membranes were conspicuous findings. No evidence, indicating the participation of lysosomes in the development of cellular damage, was obtained. Secretory granules were prominent and well preserved even in cells which showed advanced necrosis. The failure of discharge and degradation of secretory granules in the necrotic cells suggest that factors accounting for their intracellular migration and extrusion are very sensitive to ischemia and are paralyzed at an early phase.
Pituitary glands obtained at autopsy from 20 male and 20 female subjects, over 80 years of age, have been investigated with various staining procedures, including the immunoperoxidase technique for the cytological localization of prolactin. Prolactin cells were numerous and well developed in the anterior lobes. The incidence, distribution, granulation and immunoreactivity of prolactin cells showed no apparent difference between old male and female subjects dying of acute or chronic illnesses. It can be concluded that prolactin cells do not regress in old age. The morphologic findings are consistent with the assumption that the pituitary gland is capable of secreting prolactin in aging subjects.
Fine-structural study of large, vacuole-like structures of the human corticotroph cell ('enigmatic body'; EB) revealed that these bodies have a preferential juxtanuclear position in the vicinity of the Golgi complex. EBs have rugged outlines, frequently a narrow electrondense rim and numerous membrane-bound compartments in an almost homogeneous matrix of low electron density. Fusion between EBs and secretory granules and other cytoplasmic components was noted. The peripheral rim and the matrix exhibited moderate to strong acid phosphatase activity. The inner compartments were consistently negative. It is proposed that EBs represent special lysosomes and serve as centers for recycling secretory material, as well as for storage and release of degraded products.
The fine structure of centriolar precursors was studied in three human neoplasm: a chief cell adenoma of the parathyroid, an undifferentiated cell adenoma of the pituitary and a malignant lymphoma of the thyroid arising in Hashimoto's thyroiditis. Morphological evidence has been presented in support of the view that micochondria may serve as progenitors of centrioles. The sequence of events of mitochondrial centriole formation, from the early accumulation of electron dense substance at one pole of the mitochrondrion to the fully developed organelle, is documented. The findings indicate that centriolar abnormalities, such as multiplicity, accumulation or precursors, etc., may occur in benign and malignant, epithelial and mesenchymal tumors showing no apparent correlations with the biological behaviour of the neoplasms.
A 49-year-old man with pancreatic adenocarcinoma, suggestive of islet cell origin, showed clinical and biochemical features of ectopic ACTH syndrome and underwent bilateral adrenalectomy. Light microscopy revealed adrenocortical compact cell hyperplasia and lipid depletion. The zona glomerulosa was detected in small foci and fasciculata cells extended up to the capsule. Electron microscopy disclosed enlargement of adrenocortical cells, massive SER accumulation, RER increase, lipid depletion, prominence of the Golgi apparatus and development of complex interdigitations between closely apposed cell membranes. These changes were attributed to the stimulative effect of ACTH discharged from the non-pituitary tumor. Mitochondria exhibited enlargement, pleomorphism and cavitation. Most of the adrenocortical cells contained mitochondria with vesicular cristae--a characteristic feature of fasciculata cells. In a few cells, under the capsule, some mitochondria possessed lamellar cristae. Gradual transformation to the vesicular type was, however, apparent indicating that mitochondria are not rigidly constant structures.
A single injection of vinblastine given i.v. to rats lead to the disappearance of microtubules, development of crystalline inclusions, dilation of Golgi sacculi, formation of multivesicular bodies and cytosegresomes as well as accumulation of lysosomes in the cytoplasm of liver cells. The endoplasmic reticulum and mitochondria do not seem to be affected. The question of whether or not these fine structural alterations are causally related has yet to be elucidated.
Among 87 pituitary adenomas, four neoplasms had a superficial resemblance to undifferentiated cell adenomas and some fine structural features of both sparsely granulated adenomatous growth hormone and prolactin cells. Misplaced exocytosis, fibrous bodies, and multiple centrioles were sometimes revealed within the same cell and usually were accompanied by oncocytic transformation, mitochondrial alterations, and abnormal centriologenesis. The patients had normal or low blood growth hormone levels and elevated or normal prolactin values. All the tumors that were tested contained immunoreactive growth hormone and prolactin, irrespective of the blood hormone levels. The four tumors could represent a hitherto unclassified adenoma type and derive from the common, committed precursor of the two acidophils. The term acidophil stem cell adenoma is proposed to designate this entity.
Pituitary adenomas arise from and consist of adenohypophyseal cells. Based on the tinctorial characteristics of the cell cytoplasm, they were divided previously into chromophobic, acidophilic, and basophilic adenoma types. This classification is only of limited value, since it fails to consider the endocrine function of the adenoma cells and the cell type from which the tumor originates. Advanced morphologic techniques, including electron microscopy and immunocytology, led to a new pituitary adenoma classification reflecting current knowledge and attributing greater significance to clinical features, structure-function relationships, and cytogenesis. The morphologic study of pituitary adenomas is still in a relatively early stage and much more work is required to understand the basic principles of pituitary cytopathology. Thus, the classification used in this review may change as new facts accumulate. We feel justified to say that attempts to correlate structural features of pituitary adenomas with secretory activity and their separation into distinct entities cannot be regarded as examples of curiosity-oriented research. This type of investigation represents not only an intellectually rewarding experience, but is also of practical value and provides important information for the endocrinologists.
A new pituitary classification has been developed, based on the histologic, histochemical, immunocytologic and electron microscopic investigation of 207 pituitary adenomas removed surgically from male and female patients of various ages and different clinical symptomatology. Based principally on cytogenesis, the classification attempts to correlate the morphologic features of the tumor cells with their secretory activities, the clinical history, symptomatology, and biochemical findings. The classification consists of the following eight entities: 1) growth hormone cell adenoma; 2) prolactin cell adenoma; 3) mixed growth hormone cell-prolactin cell adenoma; 4) acidophil stem cell adenoma; 5) corticotroph cell adenoma; 6) thyrotroph cell adenoma; 7) gonadotroph cell adenoma; 8) undifferentiated cell adenoma, including oncocytoma. Prolactin adenomas were found to be the most frequently occurring pituitary adenoma type.
Electron microscopy of 13 pituitary prolactin cell adenomas, removed at autopsy from untreated female aging Long-Evans rats, revealed the presence of annulate lamellae in 3 tumors. No annulate lamellae were detected in 10 non-tumorous pituitary glands of adult untreated rats. Direct continuity was demonstrated between annulate lamellae and rough-surfaced endoplasmic reticulum, consistent with the assumption that annulate lamellae may originate from and/or transform to endoplasmic reticulum membranes. The results indicate that annulate lamellae are not uncommonly formed in prolactin cell adenomas, i.e. in cells which have a faster growth rate than non-tumorous adenohypophysiocytes.
Testicular tissue was investigated by electron microscopy in a case of testicular feminization. The seminiferous tubules were lined by spermatogonia and by Sertoli cells. Spermatocytic maturation was not observed. Leydig cells were numerous and contained well developed, abundant vesicular smooth-surfaced endoplasmic reticulum and large mitochondria with tubulovesicular cristae. Reinke crystalloids were absent. The ultrastructural findings were consistent with the assumption that Leydig cells were under adequate stimulation and were in a stage of active secretion. Hence, the results seem to indicate that testicular endocrine function was maintained in the studied case.
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