Biomedical subjects
Publications and source records attributed to K J Lewin.
We report a patient with a lingual mass clinically diagnosed as lingual thyroid. Due to marked distortion of the normal thyroidal architecture from prior 131I therapy, pathological examination of the mass was consistent with a mixed salivary gland tumor. Immunoperoxidase staining for thyroglobulin was utilized to correctly characterize the lingual mass as ectopic thyroid.
Three patients with biopsy proven histiocytosis X who developed a clinical and pathological picture compatible with sclerosing cholangitis are reported. In one patient, operative biopsy of the common bile duct revealed histiocytosis X in the granulomatous/xanthomatous phase. At necropsy, however, only fibrosis of the biliary tree was seen, a picture consistent with sclerosing cholangitis. Fibrotic obstruction of the biliary tree led to death from liver failure in all three patients. The aetiology of primary sclerosing cholangitis is unknown and may be multifactorial. Perhaps involvement of the biliary tree by histiocytosis X is one cause.
Primary gastrin cell hyperfunction of the gastric antrum as a clinical syndrome consists of basal hypergastrinemia, an exaggerated gastrin response to feeding, the absence of any ectopic source of gastrin secretion, and peptic ulcer disease. The number of G-cells were quantitated in the gastric antrum of five patients with clinically diagnosed primary G-cell hyperfunction, and the results were compared to controls with a variety of gastric diseases. Patients with the clinical diagnosis of primary G-cell hyperfunction had a significantly increased number of antral G-cells (p less than 0.05). The clinical syndrome of primary G-cell hyperplasia appears to be associated with hyperplasia of G-cells rather than with the hypersecretion of gastrin by a normal number of G-cells.
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Antisera raised against serotonin, gastrin, somatostastin, motilin, bombesin, calcitonin, secretin, glucagon, ACTH, neurotensin, and pancreatic polypeptide carboxyterminal hexapeptide were employed to immunohistochemically stain seven pulmonary carcinoids. Argentaffin and argyrophil stains were also performed on all cases. Serotonin-like immunoreactivity was present in four tumors, pancreatic polypeptide-like immunoreactivity in four tumors, bombesin-like immunoreactivity in two tumors and ACTH-like immunoreactivity in one tumor. The cells shown to contain neuroendocrine products constituted a minority cell population in all tumors except the ACTH-immunoreactive tumor. This study suggests that pulmonary carcinoids, like their abdominal counterparts, contain a variety of neuroendocrine products, and may produce more than one neuroendocrine product. Serotonin and pancreatic polypeptide-like immunoreactivity were the most prevalent neuroendocrine products demonstrable in this study.
The intestinal carcinoid tumors of 26 patients were stained for the presence of serotonin, gastrin, somatostatin, motilin, secretin, glucagon, pancreatic polypeptide, ACTH, and neurotensin. Argentaffin and argyrophil stains were also performed in all cases. Thirty-five separate tumors (counting metastases and multiple primaries) from the 26 patients were studied. Serotonin was present in 30 of the 35 tumors. Nineteen tumors contained serotonin only. Fourteen tumors contained multiple neuroendocrine products. One tumor contained gastrin only. One tumor did not stain immunohistochemically, but was argyrophilic. Metastatic deposits were studied in nine patients. Some metastases produced the identical neuroendocrine products as the primary tumor, whereas others produced either additional or fewer hormones than the primary tumor. Moreover, different metastases from the same primary tumor were observed to produce different hormones. Argyrophilic cells were present in all cases and were much more numerous than cells staining by immunohistochemistry. Argyrophilic cells probably contain monoamines and polypeptide hormones in addition to those studied in this series. The argyrophil stain was the best general stain in this study for the demonstration of neuroendocrine cells. Argentaffin staining was negative in ten cases that were serotonin positive and two argentaffin positive cases were serotonin negative. The carcinoid syndrome, as clinically defined by the presence of flushing and diarrhea, was noted in five patients, all of whom had serotonin-containing small bowel carcinoids. Endocrine-related symptoms were not clinically appreciated in the remaining patients.
Estrogen receptor content of breast lesions was estimated using a fluorescent cytochemical technique and a competitive protein binding assay. Of 48 cancers examined, an equal proportion contained significant quantities of receptor by either method (62.5%). The concordance between methods for individual patients was also 62.5%. A greater proportion (26%) of patients younger than 45 years of age had receptor-positive cancers using the cytochemical method than were found by the biochemical method (10%). Benign breast disease was also studied using the fluorescent cytochemical method. A greater proportion of lesions containing estrogen receptors was found compared with that cited in the literature for the competitive protein-binding assay. Because of the methodologic simplicity of the fluorescent cytochemical method, further study for routine use is indicated.
A well-differentiated colonic adenocarcinoma containing large numbers of gastrointestinal neuroendocrine cells is presented. The presence of neurosecretory granules was confirmed by electron microscopy. Immunocytochemistry showed large numbers of serotonin-containing tumor cells and lesser numbers of somatostatin, gastrin, motilin, secretin and neurotensin-containing cells. Some of these hormones are not normally present in the colon in significant numbers of cells. The presence of several cell types within a single tumor supports the concept that the normal epithelial cells of the gastrointestinal mucosa are derived from a common endodermal stem cell. There exists a spectrum of tumors ranging from the classical adenocarcinoma to the classical carcinoid, and this report identifies the position of this case within that spectrum.
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There are few detailed studies of patients with pathological hypergastrinaemia of antral origin. We have identified four patients with severe acid hypersecretion associated with peptic ulcer disease and in whom no evidence for gastrinoma or isolated retained antrum could be found. Three of these patients also had hypergastrinaemia. In two patients, one with gastric ulcers and one with duodenal ulcer disease, the hypergastrinaemia appeared to be due to antral gastrin cell hyperfunction and there was also evidence for mild antral gastrin cell hyperplasia. In the other hypergastrinaemic patient, a primary intestinal gastrin cell hyperfunction syndrome was suspected, but a hidden gastrinoma could not be excluded. The remaining patient had nearly fatal hypersecretory ulcer disease and cimetidine failed to control the hypersecretory state. In this patient the hypersecretion responded to a more potent H2 antagonist with resolution of a metabolic encephalopathy. No general pathophysiological mechanism could be identified in these patients or in larger groups of patients with gastric or duodenal ulcer disease.
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A case of pancreatic tumor with features of both an acinar cell and an endocrine cell tumor is presented. The histologic appearance of the tumor by light microscopy was consistent with the appearance of either an islet cell tumor or an acinar cell tumor. Electron microscopy revealed two distinct populations of membrane bound granules within the same tumor cells; namely, a small granule measuring 100-200 nanometers in diameter with a narrow halo separating it from the granule membrane, and a large granule measuring 400-500 nanometers in diameter and having a closely applied membrane. The smaller granules have the characteristic appearance of gastroenteropancreatic (GEP) endocrine-cell granules. The large granules are greater in size than neuroendocrine granules, their morphologic structure is most consistent with that of zymogen granules, and a positive lipase stain supported the presence of zymogen granules within the tumor. The occurrence of both neuroendocrine and zymogen granules within the same cell has been previously described in the "intermediate cell" of the pancreas, but not to our knowledge in a tumor of the pancreas. The finding of both endocrine and exocrine granules within a single cell indicates a histogenetic relationship between the pancreatic endocrine and exocrine cells, and may represent the first reported case of a neoplastic proliferation of intermediate cells.
Sixty-six consecutive liver biopsies demonstrating chronic hepatitis (CAH) were stained for the presence of HBsAg using the three-step peroxidaseantiperoxidase technique. Only cases of CAH thought to be attributable to either hepatitis B or non-A, non-B hepatitis were included in this series. Twenty-three of 30 biopsies taken from 24 patients with HBsAg-positive serum stained positively. None of the HBsAg sero-negative cases stained postively. Hepatocytes staining positively for HBsAg were generally few in number and randomly distributed within the liver lobules. Three cases of membranous staining were noted. After grading both the degree of inflammatory activity and the amount of HBsAg staining, we found that a statistically significant inverse relationship exists. The biopsies of six of the GBsAg sero-positive patients who had received steroid therapy for their liver disease did not stain differently from the biopsies of the remaining 18 HGsAg sero-positive patients. Stains for HBsAg may help in distinguishing acute hepatitis B (HB) superimposed on preexisting liver disease from hepatitis B-CAH (CAHB). This distinction may be possible because tissue staining almost always is negative in acute HB, whereas it often is focally positive in CAHB. This application of immunoperoxidase may be especially useful in patients who are drug addicts.
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The histopathologic aspects of 62 cases of chronic active hepatitis (CAH) were examined to compare hepatitis B surface antigen (HBsAg)-positive with HBsAg-negative (non-A, non-B) cases. Epidemiologically, the two groups were distinct. Homosexuals and young, male users of intravenous drugs accounted for most of the cases of hepatitis B CAH, whereas older men and women with a history of blood transfusions represented a large percentage of the HBsAg-negative cases. However, there were no pathologic differences between the two diseases, in severity of inflammatory activity, degree of architectural damage, appearance of the bile ducts, or prevalence of cirrhosis. In a population of hospitalized patients, these two diseases cannot be distinguished microscopically unless hepatocytes that contain HBsAg are demonstrated. Although our current understanding of non-A, non-B CAH is limited, the disease not necessarily remit spontaneously, and progression to cirrhosis can be expected in some cases.
We studied a case of xanthogranulomatous cholecystitis, an entity rarely described in English-language literature. Our lesion is unique with regard to the extent of involvement. It is characterized grossly by a markedly thickened gallbladder wall that is yellowish and granular. Microscopically, the gallbladder was diffusely infiltrated by foamy macrophages that contained lipofuscin, lipid material, and bile pigment, features corroborated by transmission electron microscopy. The origin and pathogenesis of xanthogranulomatous cholecystitis was reviewed. We postulate that, in the presence of obstruction and bile stasis, the combination of inflammation, tissue necrosis, and bile extravasation will lead to formation of xanthogranulomas similar to that produced in experimental pyelonephritis.
The synthesis and degradation of histamine by dog fundic mucosa was studied by using cells dispersed by enzymatic digestion and separated sequentially by velocity sedimentation in an elutriator rotor, and by density gradient. Histidine decarboxylase activity was found in appreciable amounts in fractions highly enriched in mast cells when these cells were studied intact, whereas only trace activity was detected in homogenates of these mucosal mast cells or of whole mucosa. Unlike the rat gastric mucosal histamine cell, dihydroxyphenylalanine decarboxylase activity was not present in the canine fundic mast cell. Serotonin, which is found in the rat peritoneal mast cell, was not detectable in the canine mast cell. The histamine-degrading enzyme, histamine methyltransferase, was also present in gastric mucosal cells, but not diamine oxidase. This methyltransferase activity was primarily associated with parietal cells and was not found in the mast cell-enriched functions. For comparison, fractions containing 60%-80% mast cells were enriched by elutriation from enzyme-dispersed cells of canine liver. As with the gastric mast cells, histidine decarboxylase activity was found in intact cell, but it was lost upon cell disruption.
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