Carcinoid of the pancreas: clinical characteristics and morphological features.

The classical carcinoid tumour (WHO) of the pancreas is extremely rare and its diagnosis may puzzle physicians and pathologists. Here, 29 previously published cases of pancreatic carcinoid tumours, including one new case, are reviewed. Literature research was done using MedLine from 1966 to 1995. Pancreatic carcinoids produce an atypical carcinoid syndrome. Skin flushing was reported in only 34%. The main symptom was pain, followed by diarrhoea and weight loss. Elevated urinary 5-HIAA levels were found in 85% (17/20). The immunocytochemical sensitivity for serotonin was 100% (11/11). The diagnosis of pancreatic carcinoid tumour is based on the typical endocrine histological features together with increased serotonin metabolism. Generally, the slow growth rate and late invasion of adjacent organs render local resection possible, but the high incidence of distant metastases (69%) prevents long-term survival in the majority of patients. The possible role of the Octreoscan, a new radionuclide imaging technique, is discussed with regard to this tumour entity.

Morphologic and functional substrate of thyrotoxicosis caused by nodular goiters.

The pathogenesis of nonimmunogenic thyrotoxicosis caused by nodular goiters--with the exception of true toxic adenoma--was investigated in 11 patients by means of scintigraphic, morphologic and autoradiographic technics. The basic event is the appearance, for unknown reasons, of autonomously functioning follicles which are morphologically indistinguishable from normal follicles. Four basic patterns of intrathyroidal distribution of autonomously functioning follicles are individualized: Type I = multiple individual autonomously functioning follicles scattered throughout the goiter. Type II = clustered autonomous follicles without demarcation from less active parenchyma. Type III = multiple microadenomas. Type IV = autonomous function of the majority of all follicles. In all four types, the autonomous follicles occur without recognizable relation to nodule boundaries. Scintiscans cannot predict the microstructure of these types of goiters. More than one pattern of distribution of autonomously functioning follicles may occur within a single goiter. The growth of thyroid nodules is independent of, and certainly not a prerequisite to, thyrotoxicosis. Rather, the appearance of thyrotoxicosis in this type of multinodular goiter depends on (1) the number of autonomous follicles throughout the gland and (2) their mean hormone-producing capacity per unit of time.

Follicle-forming cat thyroid cell lines synthesizing extracellular matrix and basal membrane components: a new tool for the study of thyroidal morphogenesis.

Interactions between follicular epithelial cells and extracellular matrix (ECM) are supposed to play an important role in the development and maintenance of thyroid tissue architecture. In the present study we have therefore investigated the synthesis of ECM components by a feline thyroid cell line which is able to form follicle-like structures in vitro, and also in v-ras-transfected and control-transfected sublines. Transfections were performed by lipofection with pZSR (viral Harvey ras gene; neo) and pSV2-neo (control, neo only) plasmids. We have adapted a semisolid culture system composed exclusively of polymerized alginate and therefore devoid of ECM components. Feline cells embedded in alginate gels as single cells and cultured for up to 90 days formed cell clusters within 10 days. Follicle-like structures were formed in the original cell lines and also in the v-ras- and control-transfected cells. Differences in proliferation rates were observed, the v-ras-transfected cells growing up to two to three times faster than the non-transfected cells. Immunostaining was done using rabbit first antibodies directed against mouse collagen IV, human fibronectin, laminin (tumor Engelbreth-Holm-Swarm laminin), perlecan and other ECM components. For comparison, immunostaining was also performed on cryosections of nodular goiters of six hyperthyroid cats. The cell lines and their transfected clones stained strongly positive for collagen IV and fibronectin, and positively but less strongly for laminin and perlecan. The cat goiter tissue stained positively for collagen IV, laminin, perlecan, and fibronectin, and positive staining for S-laminin (containing the beta2-chain) was seen in blood vessel walls in this tissue. In conclusion, cat cell lines grow three-dimensionally in alginate beads over several weeks, they form follicle-like structures and express the same ECM components as the native cat goiter tissue. Transfection with v-ras does increase proliferation rate, but does not fundamentally alter formation of follicle-like structures and ECM expression. Alginate gel culture is a promising new tool for the study of follicular morphogenesis, polarity, the expression pattern of ECM components and of the interaction between thyrocytes and ECM. It avoids interference caused by gels composed of ECM components.

Factor VIII-related antigen in malignant hemangioendothelioma of the thyroid: additional evidence for the endothelial origin of this tumor.

Malignant hemangioendothelioma of the thyroid gland, which most often originates in a hemorrhagic nodule, is a well-known entity in European alpine regions with endemic goiter. In other parts of the world it very rarely has been diagnosed. This tumor may display considerable morphologic variation and often has been interpreted as a variant of undifferentiated carcinoma. In 13 out of 20 thyroid tumors, classified by light microscopy as malignant hemangioendothelioma, Factor VIII-related antigen, a marker for endothelial cells, was demonstrated in neoplastic cells with the help of immunohistochemical technics applied to conventional paraffin sections. In one case, in which material suitable for electron microscopy was available, Weibel-Palade bodies were found in tumor cells. These findings add strong support to the notion of an endothelial origin of this neoplasm.

Follicular tumor in the sellar region without primary cancer of the thyroid. Heterotopic carcinoma?

A case of a follicular tumor in the sellar region is described without evidence of a primary tumor within the thyroid gland or at a site known to harbor ectopic thyroid tissue. Large amounts of thyroglobulin were readily demonstrated mainly within the colloid of the follicles. The possible development from heterotopic thyroid tissue at this unusual site is discussed.

High coincidence of Mirizzi syndrome and gallbladder carcinoma.

BACKGROUND: Mirizzi syndrome is a rare complication of long-standing cholelithiasis. It is defined as obstructive jaundice caused by external compression of the common hepatic duct by an impacted stone in the gallbladder neck. Gallstone disease and cholelithiasis-associated chronic biliary inflammation may play a causative role in the pathogenesis of gallbladder carcinoma. The purpose of this study was to investigate the coincidence of gallbladder carcinoma associated with Mirizzi syndrome. Furthermore, the diagnostic value of elevated CA 19-9 levels as indicator for a coincidental gallbladder carcinoma in this syndrome was studied. METHODS: Patient demographics, clinical findings, laboratory data, results of diagnostic studies, pathologic reports, and intraoperative findings of 1579 patients undergoing cholecystectomy were obtained from patient records and were retrospectively studied. Only patients with proven Mirizzi syndrome (i.e., extrinsic mechanical compression of the common hepatic duct by impacted gallstones, associated chronic cholecystitis, and a history of jaundice) were included in this study. RESULTS: Eighteen cases of Mirizzi syndrome (1.0%) out of 1759 cholecystectomies performed between January 1986 and March 1995 were identified. The seven male patients and 11 female patients had an average age of 74.8 years (range, 32 to 87 years). In five of these patients (27.8%) coincidental cases of gallbladder carcinoma were detected. The incidence of unsuspected malignancies in long-standing gallstone disease was 36 (2%) of 1759 and was statistically significantly different (p < 0.001) from the incidence in patients with Mirizzi syndrome (27.8%, 5 of 18). No significant difference was noted in age, gender, duration of jaundice, and type of lesions between these two groups. Tumor-associated antigen CA 19-9 level was elevated in 12 patients with Mirizzi syndrome, but it was significantly higher (p < 0.0001) in all five patients with coincidental gallbladder neoplasm and peaked at 1000 units/ml. All patients diagnosed with gallbladder carcinoma died within 18 months after operation. CONCLUSIONS: There is high association of gallbladder cancer in Mirizzi syndrome. Elevated CA 19-9 levels in this syndrome are indicative of a coincidental gallbladder malignancy. Because of this high coincidence of Mirizzi syndrome and gallbladder cancer we recommend an intraoperative frozen section of the gallbladder in all patients presenting with Mirizzi syndrome.

Expression patterns of extracellular matrix components in native and cultured normal human thyroid tissue and in human toxic adenoma tissue.

The extracellular matrix (ECM) and basement membranes (BM, a specialized form of ECM) greatly influence proliferation, differentiation, and function of cells and the structure of tissues. While a considerable amount of information is available on thyroid cellular proliferation, differentiation and function, much less is known about thyroid ECM and BM. In this study the presence of the ECM/BM components fibronectin, collagen IV, alpha1, beta1, gamma1 laminin, several laminin variants, osteonectin, and perlecan was demonstrated in cryosections of nonadenomatous and toxic adenoma human thyroid tissue. Also, positive immunohistochemical staining for collagen IV, laminin, perlecan, and fibronectin was obtained in sections of human thyroid tissue cultured in a three-dimensional (alginate) culture system. The present study provides methods and data that will facilitate the investigation of the interaction between cells and ECM in thyroid tissue.

Expression of transforming growth factor beta1, beta2, and beta3 in multinodular goiters and differentiated thyroid carcinomas: a comparative study.

The various isoforms of transforming growth factor-beta (TGFbeta) are growth-inhibiting cytokines for cells of epithelial origin. In malignant thyroid tumors, several studies documented a high expression of TGFbeta in the majority of thyroid follicular cells suggesting a possible role as an inhibitor of cell proliferation. In contrast to this uniform pattern of TGFbeta expression in thyroid cancer, scarce and controversial data have been reported on the expression of TGFbeta in benign multinodular goiter. In the present study, we therefore analyzed the expression of TGFbeta1, TGFbeta2, and TGFbeta3 in normal thyroid tissue, multinodular goiters and papillary thyroid carcinomas by immunohistochemistry. In normal thyroid tissue, expression of the 3 TGFbeta isoforms was barely detectable. However, in the carcinomas, almost all epithelial cells displayed immunoreactivity for the three TGFbeta isoforms. In the nodules from multinodular goiters, all 3 isoforms were found to be expressed although the immunolocalization of the 3 proteins was highly variable. TGFbeta-immunostaining was found in scattered clusters of variable size and, its expression pattern was heterogenous among individual cells within single follicles. TGFbeta-positivity was present in spite of immunostaining for proliferating cell nuclear antigen (PCNA), a marker for actively proliferating cells. In conclusion, this study shows that thyroid carcinomas and benign tumors express the TGFbeta1, TGFbeta2, and TGFbeta3 isoforms. In contrast to the abundant and homogeneous expression in differentiated thyroid carcinomas, TGFbeta expression displays a highly variable interfollicular and intrafollicular pattern in multinodular goiters, suggesting an important role of TGFbeta isoforms in tumorigenesis of thyroid cells.

Nuclear localization of epidermal growth factor and epidermal growth factor receptors in human thyroid tissues.

Epidermal growth factor (EGF) has widespread growth effects, and in some tissues proliferation is associated with the nuclear localization of EGF and epidermal growth factor receptor (EGFR). In the thyroid, EGF promotes growth but differs from thyrotropin (TSH) in inhibiting rather than stimulating functional parameters. We have therefore studied the occurrence and cellular distribution of EGF and EGFR in normal thyroid, in Graves' disease, where growth is mediated through the thyrotropin receptor (TSHR), and in a variety of human thyroid tumors. In the normal gland the staining was variable, but largely cytoplasmic, for both EGF and EGFR. In Graves' disease there was strong cytoplasmic staining for both EGF and EGFR, with frequent positive nuclei. Nuclear positivity for EGF and particularly for EGFR was also a feature of both follicular adenomas and follicular carcinomas. Interestingly, nuclear staining was almost absent in papillary carcinomas. These findings document for the first time the presence of nuclear EGF and EGFR in thyroid. Their predominant occurrence in tissues with increased growth (Graves' disease, follicular adenoma, and carcinoma) may indicate that nuclear EGF and EGFR play a role in growth regulation in these conditions. The absence of nuclear EGF and EGFR in papillary carcinomas would suggest that the role played by EGF in growth control differs between papillary carcinoma and follicular adenomas/carcinomas of the thyroid.

[Angiography in Crohn's regional enteritis. Its relation to conventional radiological, endoscopic and micro-angiographic findings]. / Die Angiographie bei Enteritis regionalis Crohn. Relation zu konventionell-radiologischen, endoskopischen und mikroangiographischen Befunden

There has been a definite increase in the incidence of Crohn's disease in recent years. A particular feature of this disease is the high incidence of recurrence after surgical removal of affected portions of the gut. This may be due to a resection carried out through a diseased segment and this stresses the importance of recognising early changes. This is not possible by conventional radiology (small bowel examination, barium enema) and is therefore an indication for pre-operative visceral angiography. The results obtained in ten patients, who subsequently came to surgery, were compared with the findings on conventional radiology and endoscopy. Angiography proved the best method for the early demonstration of inflammatory changes. This was confirmed by histological examination of the resected specimen.

[Hyperthyroidism in thyroid cancer. Retrospective study of 53 cases]. / Hyperthyreose bei maligner Struma. Retrospektive Erhebung mit 53 Fällen.

Hyperthyroidism was diagnosed in 53 of 273 thyroid carcinoma patients at the time of their first examination (between 1971 and 1983). This corresponds to 19.5% of these mainly well-differentiated thyroid cancers. In 24 (45%) patients the hyperthyroidism and the thyroid carcinoma were two separate distinct illnesses: of 4 patients with Graves' disease (1.5% of 273), 2 had been operated because of an additional solitary cold nodule, and in the other 2 an occult carcinoma was found intraoperatively. Twenty patients of this group had Plummer's disease: there was a malignant cold nodule within a multinodular goiter with multifocal functional autonomy (MFA)(n = 14) or a carcinoma located near the solitary hot nodule of the toxic adenoma (TA)(n = 6). In these patients the distribution of the different histologies was about the same as in other thyroid cancer patients from this region. The remaining 29 patients (55%) had Plummer's disease, 28 with the classical finding of a solitary toxic adenoma, in which the hot nodule and the malignant tumor were identical. It was possible to confirm this identity histologically in 10 out of 24 cases, retrospectively. Eight of these patients had metastases with radioiodine uptake at the time of the first examination. Of the tumors in this group, 24 were follicular and 5 papillary carcinomas. As a rough estimate, one malignant, scintigraphically hot tumor is found for every 50 benign toxic adenomas. Criteria for the differentiation are: recent growth of the nodule, tumor size of greater than 5 cm diameter or greater than 35 g and an elevated T3-level of less than 0.06 nmol/l/g tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Fatal intestinal pseudo-obstruction in brown bowel syndrome.

A 52-year-old man, suffering for years from malabsorption due to endemic sprue, developed progressive bowel dysfunction, ie, recurrent ileus and intestinal pseudo-obstruction. Because of partial volvulus formation, ileocecal resection was performed. Histopathologic examination of the resected specimen revealed signs of advanced brown bowel syndrome, with excessive deposits of ceroid-lipofuscin in, and a considerable loss of, smooth-muscle cells and myofibrils. The patient died after surgery, and at autopsy a systemic ceroid lipofuscinosis of smooth-muscle cells was detected. Neuronal ceroid lipofuscinosis was not observed. Serious and eventually fatal bowel dysfunction is rarely seen in brown bowel syndrome, but may occur in advanced stages. Since treatment with vitamin E appears to exert a favorable effect, early diagnosis of brown bowel syndrome seems to be very important.

Leiomyosarcoma of the middle ear and temporal bone.

Leiomyosarcoma is a malignant tumor of smooth muscle origin. It is rarely encountered in the head and neck area. A patient with leiomyosarcoma of the middle ear and the temporal bone with unusual bone destruction is presented. To our knowledge it is the first report of a middle ear and temporal bone leiomyosarcoma.

Biocement--a new material. Results of its experimental use for osseous repair of skull cap defects with lesions of the dura mater and liquorrhea, reconstruction of the anterior wall of the frontal sinuses and fixation of alloimplants.

A newly developed material, which we call biocement, consisting of bisphenol-a-glycidyl methacrylate ("epoxide methacrylate') as organic matrix and Bioceramic Battelle, Bioglass Hench and/or pentacalcium hydroxide triphosphate ("tri-calcium phosphate') powder as filling particles is presented. In an extension of previous experiments, various types of this biocement, containing different admixtures of particulate matter, were employed to test their usefulness in head surgery, in particular maxillo-facial reconstruction, on dogs and a rhesus monkey. Encouraging results were obtained with regard to (a) fixing a titanium alloimplant under some degree of mechanical stress; (b) covering a defect in the skull cap, including the closure of an artificially induced meningeal fistula with liquorrhea; and (c) reconstruction of defects in the anterior wall of frontal sinuses. Special emphasis is placed on direct contact between biocement and bone, interdigitations between these two, reactions of meningeal tissue, and regeneration of ciliated epithelium underneath fixed reimplants over the frontal sinus.

[Congenital cystic duplication of the stomach--a rare surgical disease]. / Die congenitale cystische Duplikatur des Magens--eine seltene chirurgische Erkrankung.

Duplication of the stomach is a rare congenital disease of the childhood. We report the exceptional manifestation in two adults. The clinical presentation and developmental theory is discussed by reviewing the literature. Today the therapy of choice is resection of the duplication with removal of the adjacent wall of the stomach.