[Intracystic papilloma of the male breast associated with monolateral gynecomastia. Clinicopathological findings in a case].
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Biomedical subjects
Publications and source records attributed to B Frigerio.
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We report the case of two patients suffered from cholestatic jaundice occurred 3-4 weeks after starting ticlopidine therapy. In both cases the diagnosis was made by ruling out any other known cause of acute hepatitis or cholestasis. One patient underwent liver biopsy, which showed a typical intralobular cholestatic pattern and a slight lymphocytic infiltration of the portal tracts. The other patient, a 29 year-old woman, was taking ticlopidine as the sole drug, further to an ischemic stroke occurred while she was taking oral contraceptives; she presented a diffuse itchy dermatitis, fever and slight eosinophilia besides cholestasis. In both patients ticlopidine was discontinued and liver tests returned to normal values within 4-8 weeks; no rechallenge was attempted and ticlopidine was replaced with another antiplatelet drug. To the best of our knowledge 19 cases of ticlopidine-related cholestatic disease have been described so far in the literature. Its pathogenesis is still unknown, although some clinical findings and experimental results from patients with acute enteropathy or agranulocytosis induced by ticlopidine suggest that the drug may act through a toxic mechanism, perhaps mediated by prostaglandins.
Cytogenetic analysis of primary cell cultures from human atherosclerotic fibrous plaques revealed clonal chromosome abnormalities in 13 of the 18 cases studied. Loss of the Y chromosome and del(13)(q14) were present as single clonal abnormalities in eight cases; in five cases separate clones were found involving loss of the Y and a XXY karyotype, trisomy 10 and 18, loss of the Y and trisomy 7. A variety of single numerical and structural abnormalities were present in all but two of the 18 cases. Immunocytochemical studies were performed on cells from the same cultures used for cytogenetic analysis using monoclonal antibodies to human leucocyte common antigen, to human vimentin and to muscle actin. The immunoreactivity was positive for actin in 70-80% of the cells; 100% of the cells were positive for vimentin and all cells were ALC negative. These results indicated that the chromosomal abnormalities are present in the smooth muscle cells of the plaque. The hypothesis is proposed that the proliferation leading to the atherosclerotic lesion may primarily represent a hyperplastic response to mechanical and biological injuries and that this reactive proliferation is, in turn, associated with a tendency to chromosome instability.
It has been found by immunohistochemical staining that antigens normally found in gastric and/or intestinal epithelial cells are expressed in most differentiated duct cell carcinomas of the pancreas. Among 88 such tumors, 93% and 92%, respectively, expressed M1 and cathepsin E, markers of gastric surface-foveolar epithelial cells, 51% expressed pepsinogen II, a marker of gastroduodenal mucopeptic cells, 48% expressed CAR-5, a marker of colorectal epithelial cells, and 35% expressed M3SI, a marker of small intestinal goblet cells. Most of the tumors also expressed normal pancreatic duct antigens; 97% expressed DU-PAN-2, and 59% expressed N-terminus gastrin-releasing peptide. In agreement with these findings, electron microscopy revealed malignant cells with fine structural features of gastric foveolar cells, gastric mucopeptic cells, intestinal goblet cells, intestinal columnar cells, pancreatic duct epithelial cells, and cells with features of more than one cell type. Normal pancreatic duct epithelium did not express any marker of gastrointestinal epithelial cells, whereas such benign lesions as mucinous cell hypertrophy and papillary hyperplasia commonly expressed gut-type antigens but rarely expressed pancreatic duct cell markers. By contrast, lesions characterized by atypical papillary hyperplasia commonly expressed both gastric and pancreatic duct cell markers. Metaplastic pyloric-type glands expressed pepsinogen II and, except for their expression of cathepsin E, were indistinguishable from normal pyloric glands. In marked contrast, the immunohistochemical and ultrastructural features of 14 ductuloacinar cell tumors were those of cells lining terminal ductules, centroacinar cells, and/or acinar cells; none expressed any gut-type antigen. The results indicate that gastrointestinal differentiation is common in both benign and malignant lesions of pancreatic duct epithelium and suggest that duct cell carcinomas are histogenetically related to gastric- and intestinal-type metaplastic changes of epithelial cells lining the main and interlobular ducts of the pancreas.
The results of histopathological, histochemical and ultrastructural investigations on pheochromocytomas and paragangliomas have been reported. These results allowed the functional identification of the cell types composing many of such tumours. Moreover, comparison of these data with clinico-pathologic findings outlined the advantages and limits of cytologic studies for understanding the natural history of pheochromocytomas and paragangliomas and improving our diagnostic and prognostic criteria.
Gastrectomy specimens of 148 gastric cancers, 40 of them being intramucosal or microinvasive, 27 penetrating the submucosa and 81 invading the muscularis propria, with or without involvement of the serosa and perigastric tissues, have been investigated with conventional histopathologic techniques, mucin histochemistry and electron microscopy to characterize the various lines of tumour cell differentiation and to correlate these with the histologic patterns of tumour growth. More or less differentiated intestinal columnar, intestinal goblet, gastric foveolar or mucopeptic cells were recognized in most tumours, of glandular, diffuse or mucoid type. Although simultaneous expression of more than one cell type into the same tumour occurred very frequently, intestinal columnar cells were more prominent in tubular adenocarcinomas, goblet cells (especially of colorectal type) in mucoid cancers, mucopeptic cells in diffuse cancers of invasive desmoplastic type and foveolar cells in diffuse cancers of intramucosal signet-ring cell type. In general, an increased tendency to foveolar cell differentiation and a reduced tendency to mucopeptic differentiation has been found in intramucosal cancers as compared to invasive cancers. It is concluded that the type of tumour cell differentiation, which might have some influence on the natural history of gastric cancer, is better related with more defined tumour subtypes than with the usually recognized glandular or diffuse patterns.
A 13-month-old boy with intermittent preexcitation (Lown-Ganong-Levine type) and paroxysmal tachycardias of 280 to 300 beats per minute died suddenly with cardiac arrest. At necropsy the only abnormalities were in the heart. There were multifocal Purkinje cell tumors in the conduction system, including one directly at the bifurcation of the His bundle. In addition, a fault in the central fibrous body was filled with an accessory communication between the mid-portion of the atrioventricular node and both the interventricular septum and the His bundle. This accessory communication connected with the Purkinje cell tumor. Although an atrioventricular nodal bypass was thus present and could account for the preexcitation and for reentrant tachycardias, there is also the anatomic basis for an automatic arrhythmia originating within one or more of the Purkinje cell tumors, particularly the one directly within the His bundle. Dispersion of elements of the conduction system within the central fibrous body resembled the normal fetal pattern. Whether this persistence of fetal dispersion of the atrioventricular node and His bundle within the central fibrous body is causally related to the presence of multifocal Purkinje cell tumors or is only coincidence merits further consideration.
We report a case of small-cell (oat cell) carcinoma of the endometrium in a 59-year-old woman. The tumor was confined to a portion of an adenomatous polyp. It exhibited argyrophilia with Grimelius' stain and dense-core endocrine-type granules by electron microscopy. The patient was alive and well one year later. To our knowledge, this is the fourth reported case of a small-cell carcinoma of the endometrium exhibiting endocrine differentiation.
Secretin has been localized by the immunogold technique in endocrine cells of the dog duodenum--previously described as "K cells"--characterized by secretory granules with double structure consisting of a secretin-containing osmiophilic core surrounded by an argyrophil halo. Granules resembling those of dog secretin cells were also found in some ultrastructurally characterized S cells of the cat, pig, rat and rabbit duodenum, thus confirming in these species the identification of S cells with secretin cells. Conversely, the cells previously described as "S cells" in the dog lacked secretin immunoreactivity.
Three cases of gastric parietal cell carcinoma are described. Tumour cells are round to polygonal, with abundant eosinophilic, granular cytoplasm reactive with phosphotungstic acid haematoxylin and Luxol Fast Blue. Ultrastructurally the tumour cells are characterized by abundant mitochondria, tubulovesicles, intracellular canaliculi and intercellular lamina filled with undulated microvilli.
A series of 15 Merkel cell tumours of skin is reported. They occur dominantly on the head and neck and on the extremities of elderly women, frequently presenting as a reddish nodule. Three cases were associated with squamous carcinoma at the same site, an association deserving further study. There are two main patterns: the commoner one takes the form of a trabecular carcinoma in the dermis mimicking metastatic carcinoma, including oat-cell carcinoma and neuroblastoma: a dissociated-cell form mimicks malignant lymphoma. The triad of vesicular nuclei with very small nucleoli, abundant mitotic activity and apoptosis is so characteristic as to be virtually pathognomonic in conjunction with structural features. Argyrophilia is common, but Bouin fixation is necessary to demonstrate it regularly. Small round secretory granules (89 +/- 18 nm) with narrow haloes, and an abundance of intermediate size filaments are among the ultrastructural hallmarks. There is a close similarity between better differentiated tumour cells and normal Merkel cells. The neural crest origin of MC is in doubt both on the basis of studies of the development and regeneration of MC and from the study of Merkel cell tumours.
A group of 33 functionless pituitary tumors with small argyrophil groups (SAG) were collected from a series of 200 pituitary adenomas (16.5% of all adenomas). Histologically, the tumors showed an unusually high frequency of trabecular patterns, perivascular pseudo-rosettes, and oncocytoid transformation. Immunoreactivity for glycoprotein hormone alpha-chain was found in more or less numerous cells of 20 cases (64.5% of SAG tumors). Thirteen of these cases also showed specific beta-chain immunoreactivity, especially for follicle-stimulating hormone (FSH) beta-chain, which was present in 11 tumors. Various admixtures of immature, oncocytic, sparsely granulated, and densely granulated cells were observed ultrastructurally, with prevalence of the latter cell variants in tumors showing immunoreactive cells and prevalence of the former cell variants in tumors lacking immunoreactive cells. It is suggested that some relationship may exist between SAG cell (glycoprotein hormone precursor cells?) tumors--or at least part of them--and glycoprotein hormone cell lines. Anyway, whatever their origin and interpretation, SAG cell tumors seem to represent a distinct clinicopathologic entity.
A case of primary malignant laryngeal carcinoid with dual endocrine and mucous differentiation is reported. Histologically the tumor showed a characteristic organoid pattern and exhibited Alcian-blue, periodic acid-Schiff, and Grimelius silver positivity. By the immunoperoxidase technique calcitonin, ACTH, and alpha-hCG subunit were demonstrated in the tumor cells. Electron microscopy revealed two different types of endocrinelike cells: mucous cells and occasional cells containing both endocrinelike granules and mucin droplets. Diagnostic morphologic criteria of this rare tumor entity are discussed and reference to biologic behavior and possible histogenesis is made.
The argyrophil reaction occurs in the parathyroid cells with the Grimelius silver nitrate stain. In the present study, Bouin's fluid was found to be superior to other tested fixatives (formalin, Karnovsky's fluid, GPA etc) in this respect. A study of the argyrophil reaction on the ultrastructural level showed an accumulation of silver particles in the secretory granules, which means that the Grimelius silver stain can be assumed to be an indicator of the secretory granules stored in the parathyroid cells. Whether the argyrophil reaction can be of help in differential diagnosis between different abnormal parathyroid conditions is not yet clear.
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Two types of endocrine-paracrine (EP) cells have been detected histochemically and ultrastructurally in normal and hyperplastic prostates; i.e. type I cells resembling intestinal EC (enterochromaffin) cells and type 2 cells similar to urethral EP cells previously reported by Casanova et al. (1974). About one-third of the 40 prostatic carcinomas studied contained EP cells: two of these were composite tumours exhibiting both adenocarcinomatous and carcinoid patterns. These four tumours have also been studied histochemically and ultrastructurally. ACTH and beta-endorphin immunoreactive cells, ultrastructurally resembling pituitary corticotrophic cells, have been identified in three tumours. Cells identical with type I and type 2 cells of the normal prostate were detected in two cases and in a further case, respectively.
At least 16 types of endocrine-paracrine cells have been identified ultrastructurally in the gastrointestinal mucosa. The production of hormones and local messengers such as 5-hydroxytryptamine, gastrin, cholecystokinin, somatostatin, secretin, gastric inhibitory peptide (GIP), enteroglucagon (glicentin, GLI), motilin, neurotensin, substance P and the enkephalins, by these cells, has been established. Progress has also been made in cytological studies of gut and pancreatic endocrine tumours. Argentaffin EC cell carcinoids, gastrinomas (of several ultrastructurally different varieties of gastrin cells), L-cell tumours and D-cell tumours are among those cytologically and functionally defined in the gut. Functionally undefined tumours include the so-called non-argentaffin carcinoids arising in various parts of the gut, some of which have been characterised cytologically as gastric ECL cell tumours and gastroduodenal P-D1-cell tumours. Gastrinomas, vipomas and rare argentaffin carcinoids are among gut-related pancreatic endocrine tumours. Non-functional paragangliomas, usually with some neuromatous component, occur in the duodenal wall. Extrapancreatic vipomas display ultrastructural features of ganglioneuroblastomas with peptidergic granules.
Among 74 histochemically and ultrastructurally studied pituitary adenomas, 12 apparently chromophobe tumors were characterized by the presence of numerous argyrophil cells. All these argyrophil adenomas failed to reveal presence of GH, prolactin or ACTH cells. Two tumors were found to consist of well granulated cells reacting intensely with anti-TSH antibodies and resembling TSH cells of the normal pituitary. The remaining argyrophil adenomas did not show TSH immunostaining and, with one exception, failed to react with an anti-HCG serum staining gonadotroph cells of human pituitary. They were composed of small, closely apposed cells with small compact or vesicular granules. These tumor cells seem to correspond to some small argyrophil cells found in non-neoplastic pituitary, which differ from TSH cells and from all other types of functionally identified adenohypophyseal cells.