Search PubMed⌕ Search

Biomedical subjects

W Saeger

Publications and source records attributed to W Saeger.

At least 73 records · Page 4Linked to original sources

Corpora amylacea in the lung, prostate and uterus. A comparative and immunohistochemical study.

Previous studies have shown that corpora amylacea (CA) in certain organs, including the prostate, lung and uterus, are composed of amyloid. This observation raises the question of whether these amyloid deposits share a common origin or demonstrate the diversity which characterizes other amyloid syndromes. Sections of the lung, prostate and uterus from 110 consecutive autopsies of individuals over 84 years of age were studied initially using H & E and Congo red staining. CA were present in 54 cases (49%) with the prostate affected in 23 cases, the lung in 19 cases and the uterus in 15 cases. Immunohistochemistry with a panel of antibodies directed against the major amyloid fibril proteins, i.e. AA, A beta 2M, A lambda, A kappa and ATTR, yielded strong immunoreactivity of prostatic and pulmonary CA with anti-A beta 2M. Immunostaining with an antibody against cytokeratin (KL1) gave a weak reaction in a single case of prostatic CA, indicating that it is unlikely that these CA derive from cytoskeletal remnants of shedded epithelial cells. The uterine CA were not stained by any of the antibodies, suggesting that they have a different origin than prostatic and pulmonary CA. The influence of the local calcium concentration and niduses on the pathogenesis of CA is discussed.

Aged↗

The classification of amyloid deposits in clinicopathological practice.

A series of 104 biopsy cases with histopathological proof of amyloid, submitted to our department of pathology over the last 19 years, were re-examined. The survey investigated the medical indication for surgery, the origin and quality of the biopsy and the clinical information as documented on the request form for histopathological examination and in hospital records. Amyloid deposits were classified using antisera directed against five major amyloid fibril proteins, i.e. AA, ATTR, A lambda, A kappa and A beta 2M and optimal conditions were sought for the reliable and early characterization of amyloid disease in clinicopathological practice. This survey revealed that 98% of the biopsy cases already suffered from a disease which was either a cause or a result of amyloidosis. In only 2% of the biopsy cases was amyloidosis detected without any clinical indication. Immunohistochemical classification of the amyloid deposits and comparison with hospital records demonstrated diagnostic pitfalls such as immunostaining of amyloid by two or more antibodies recognizing different fibril proteins, and disagreement between immunohistochemical typing of amyloid and the initial clinical diagnosis. Based on these observations we assume that the characterization of amyloid disease and its biological significance is impossible in clinicopathological practice without clinical information or without immunohistochemical classification of the fibril protein in biopsy specimens. Different aspects of histopathological detection of AA- and AL-amyloidosis are discussed.

Adult↗

Portal amyloid: novel amyloid deposits in gastrointestinal veins?

OBJECTIVE: To specify uncharacterized amyloid deposits in gastrointestinal vessels of the elderly. MATERIALS AND METHODS: The gastrointestinal tracts from 110 consecutive autopsies of individuals aged 85 years and older were examined for amyloid using Congo red staining. Immunohistochemical classification of the amyloid deposits was conducted using antisera directed against amyloid A, apolipoprotein A-I, apolipoprotein A-II, apolipoprotein B, apolipoprotein C-I, lysozyme, lambda and kappa light chain amyloid fibril proteins, transthyretin, beta2-microglobulin, and amyloid P component. Electron microscopic examination assessed the ultrastructural features. RESULTS: Thirty-eight (35%) of the 110 cases had gastrointestinal amyloid deposits. In 17 cases the amyloid fibril proteins were defined immunohistochemically. In five cases (5%) the amyloid could not be classified because amyloid deposits were not present in the deeper serial sections used for immunohistochemistry. In 13 cases (11%) the vascular amyloid deposits could not be characterized because they did not demonstrate immunoreactivity with any of a panel of antibodies specific for the fibril proteins of all major extracerebral amyloids. In three individual cases, the vascular amyloid deposits showed variable immunoreactivity, with deposits being negative in some vessels. The immunohistochemically nonreactive vascular amyloid in these 16 cases had several consistent features: it affected only vessels of the small and large intestine, it was limited to mesenteric veins, it consisted of small dot- or comma-like deposits located in close proximity to fragmented elastic fibers, and it demonstrated inconsistent immunostaining for amyloid P component. CONCLUSIONS: The similar morphologic characteristics of nonreactive gastrointestinal amyloid deposits, which we have designated "portal amyloid," suggest a common origin. Determination of whether portal amyloid represents a new type of amyloid will require chemical analysis.

Aged↗

Adrenocortical nodules in post-mortem series. Development, functional significance, and differentiation from adenomas.

In 498 consecutive autopsy cases, the adrenal glands were light microscopically and morphometrically studied. 265 (53.7%) patients showed single or multiples nodules, 25 (5.0%) adenomas. The diameter of nodules was between 0.3 to 8.0 mm and that of adenomas between 3.2 to 28.0 mm. Clinically, 265 (36.5%) patients revealed arterial hypertension. 283 (63.5%) were normotensive. For the diagnosis of adenomas, the architecture and the cell structure were more important than the size of the tumor. Normotensive patients showed more often (55.%) nodules than hypertensive patients (52.8%). Adenomas were more frequently found in hypertensive patients. There was no correlation between age, sex and nodules, but adenomas were more frequently found in females. Normotensive patients exhibited mainly one nodule, whereas multiple nodules were found in hypertensive patients. In patients with nodules arteriosclerosis with intima hyalinosis was present in 184 (56.3%) cases, in patients without nodules in 81 (47.4%) cases. Our study clearly demonstrates that no correlation exists between the occurrence of adrenocortical nodules and age or hypertension. The etiology of adrenal nodules should be considered together with the arteriopathy.

Adenoma↗

[Urine examination for tumor cells using quantitative immunocytochemistry. Antibodies to a CEA-like antigen].

A total of 39 specimens of urine were tested for tumor cells using a monoclonal antibody (mab 486p 3/12, "medaquic"). Of these specimens, 18 were obtained from patients with histologically confirmed transitional cell carcinoma. All these specimens were also examined morphologically for the presence of atypical cells, and 25 specimens using a monoclonal antibody against CEA. The "medaquic" test showed a 77.8% sensitivity for detecting transitional cell carcinoma (conventional cytology: 61.1%). The percentage of false-positives with the "medaquic" test was 33.3% (2/6): the results of conventional cytology were similar; two GI carcinomas were not detected by "medaquic". The antigen for the mab 486p 3/12 is a CEA-like glycoprotein. The "medaquic" test was positive appreciably more often than was the CEA antibody reaction.

Antibodies, Monoclonal↗

Hypophysitis in surgical and autoptical specimens.

We present the clinical and histological findings of 11 cases of inflammatory anterior pituitary lesions, 8 of which were obtained during surgery and 3 of which were obtained from autopsies. Additionally, we extended the conventional classification of pituitary inflammatory disease by the new entity " secondary hypophysitis". Of the surgically obtained specimens 5 consisted of inflammatory extension into the pituitary gland out of the surrounding tissue. In all of these patients the inflammation originated from an additional tumor in the sellar region (4 craniopharyngiomas, 1 prolactinoma). These will be referred to as "secondary hypophysitis", an entity which has not yet been mentioned in the literature. Of the remaining 6 cases, 2 were granulomatous hypophysitis, 2 pituitary abscesses, 1 lymphocytic hypophysitis, and 1 showed extensive scarring of the anterior pituitary lobe due to preceeding lymphocytic hypophysitis. At histological examination the basic structure of the anterior pituitary was maintained in all cases. Relative counts of hormone-producing cells were normal. In secondary hypophysitis, the affected area was composed of fibrous tissue and granulation tissue. B and T lymphocytes were present in equal amounts. Granulomas were not found. Inflammatory infiltrates, granulation tissue and fibroses were seen in different proportions. Based on our results and three other cases reported in the literature so far, we think that the presently used classification of pituitary inflammatory diseases lacks an entity which describes a non-abscess-forming inflammation of the pituitary gland originating from an associated pathological process. Therefore, we introduced the term secondary hypophysitis to describe this fourth entity of pituitary inflammatory disease.

Adult↗

Morphology, immunohistochemistry and morphometry of the thyroid gland in cases of sudden infant death syndrome (SIDS).

The thyroid glands of 107 SIDS victims (sudden infant death syndrome) have been studied. Controls consisted of 20 thyroid glands from infants who died of other causes (accidents, pneumonia etc.). The thyroid glands were investigated histologically, immunohistologically and morphometrically. Immunohistochemistry (S-100 protein and calcitonin) and morphometry showed no significant results. Histologically, hyperemia (severe: 34 cases = 31.8%; mild: 23 cases = 21.5%), and fibrosis (45 cases = 42.1%; mild: 26 cases = 24.3%) were found. A large number of cases showed depleted follicles (87 cases = 81.3%), little colloid (little: 37 cases = 34.6%; none: 9 cases = 8.4%) and desquamation (severe: 21 cases = 19.6%; abundant: 20 cases = 18.7%). Only fibrosis and depleted follicles were found more often in SIDS than in the controls (conditional logistic regression: rise of incidence for SIDS 2.9 times, P = 0.028, and 1.2 times, P = 0.051, respectively), a commoner occurrence of hyperemia in SIDS was of limited significance (P = 0.105). The alterations found can be taken as stress reactions to current or recurrent hypoxemia and the mild fibrosis indicates recurrent hypoxemia. All alterations indicate that the victims had previously suffered near death episodes. Even though the glands were handled with care, artefacts and autolysis must be taken into consideration. Neither the histological, immunohistological nor morphometrical studies of the thyroid gland gave an explanation as to the cause of death or showed any changes providing explicit help in diagnosing SIDS.

Calcitonin↗

[Prolactin producing hypophyseal carcinoma. Case report of an extremely rare metastatic tumor].

A 59-year-old male patient was transnasally operated on because of a pituitary adenoma with hypopituitarism. A second operation and X-ray therapy followed a half year later due to recurrent tumor. Both neoplasmas were classified as sparsely granulated prolactin cell adenomas. Immunohistochemical studies revealed strong immunoreactivity for prolactin and FSH in the tumor cells of both the pituitary adenoma and the recurrent tumor. Two years later the prolactin plasma levels were extremely elevated. A tumor in the liver was identified. Biopsy revealed a solid endocrine tumor containing prolactin by immunohistology. Due to structural and immunohistological similarities this tumor could be identified as a metastasis of the pituitary tumor. After 5 months of therapy the patient died from thrombembolism. Post-mortem studies confirmed the diagnosis of a metastasizing prolactin-secreting pituitary carcinoma. Only six similar cases have been reported in the literature. Our case report confirms the experience with 35 definite pituitary carcinomas reparted in the current literature: malignant pituitary tumors develop after pituitary surgery and can be identified not from the pituitary tumor, but only from its metastases.

Combined Modality Therapy↗

Gliomatosis peritonei combined with mature ovarian teratoma: immunohistochemical observations.

Gliomatosis peritonei (GP) is the metastatic implantation of glial cells within the peritoneal cavity of patients with ovarian teratomas. The case of a young woman is presented, who initially developed a mature teratoma in the left ovary that was surgically removed. Nine years later a mature teratoma in the right ovary was excised, upon which GP was found in the greater omentum. To identify the cellular composition of the ovarian teratoma and of the omental implants, immunostainings were performed using antibodies against glial and neuronal antigens as well as against determinants of hematopoietic cells. In the teratoma the neuroectodermal part was strongly HNK-1-positive and contained GFAP- and vimentin-positive astrocytes and some NSE-positive neuron-like cells. In addition, neuroectodermal tissue was infiltrated by numerous CD68-positive macrophages/histiocytes and CD20-positive B lymphocytes. The omental nodules consisted of astrocytes, which expressed GFAP, vimentin and desmin. The implants also contained macrophages/histiocytes, which exhibited morphologic features reminiscent of microglial cells. In GP, macrophages might release glia-promoting trophic factors, which could allow the neural component of ovarian teratoma to implant in the peritoneal cavity and survive there for many years. Macrophage-derived factors might induce astroglial differentiation, which could explain why the peritoneal implants are mostly mature even when they originate from immature teratomas.

Adolescent↗

Gangliocytomas of the sellar region--a review.

Gangliocytomas are benign, slow growing neuronal tumors and are found for the most part in children and young adults. They are most often localized in either the spinal cord or the cerebral hemispheres. Gangliocytomas in the sellar region are extremely rare and only 43 such tumors (including 4 own cases) have ever been described in the literature. Although these tumors are genuine rarities without any epidemiological importance, they do provide some interesting information on tumorigenesis of pituitary adenomas: 65% of the sellar gangliocytomas are associated with a pituitary adenoma. 74% of patients with these tumors suffered hormonal oversecretion of at least one of the pituitary hormones (mostly growth hormone). With only one exception, the hypothalamic releasing hormone corresponding to the hormonal oversecretion syndrome could be demonstrated in the gangliocytoma immunohistochemically. Ultrastructural studies could demonstrate close cell to cell contacts between adenoma and gangliocytome cells. All these data support the hypothesis that chronic overstimulation by hypothalamic releasing hormones play a role in the development of hormone secreting pituitary adenomas. However, in contrast to sellar gangliocytemas, extrahypothalamic tumors secreting excessive hypothalamic hypophysiotropic hormones have never been associated with a pituitary adenoma. They have only been associated with pituitary cell hyperplasia. Therefore, the hypothesis can be made that hypothalamic releasing hormones only promote but do not initiate tumorigenesis of pituitary adenomas.

Adult↗

Interstitial amyloid deposits in the pituitary gland. Morphometry, immunohistology, and correlation to diseases.

The prevalence and immunoreactivity of interstitial amyloid deposits of the pituitary glands of 109 consecutive autopsies of individuals over 84 years of age were studied using Congo red staining and antibodies directed against the major amyloid fibril proteins and pituitary hormones. In addition, the amount of interstitial amyloid formation was evaluated quantitatively and compared with all autopsy-related and clinical diagnoses available. Eighty-seven (80%) of the 109 cases exhibited interstitial amyloid deposits in the anterior lobe. All reacted immunohistochemically with antiamyloid lambda light chain and antiamyloid P-component. Quantitative analysis in 62 cases revealed a mean volume percentage of interstitial amyloid in the anterior lobe of 0.56%. In statistical analysis, only two of the 25 diseases recorded were associated with interstitial amyloid: chronic obstructive pulmonary disease and non-insulin-dependent diabetes mellitus. The prevalence of chronic obstructive pulmonary disease correlated positively with the occurrence (chi 2; P < .02) as well as with the amount of amyloid (Wilcoxon; P < .04) in the pituitary. In addition, non-insulin-dependent diabetes mellitus was accompanied with higher amounts of interstitial amyloid than with all other disorders (Wilcoxon; P < .03). Until now, a correlation was proposed only between non-insulin-dependent diabetes mellitus and islet amyloidosis of the pancreas.

Aged↗

Pathology of adrenal neoplasms.

The use of immunohistochemistry and electron microscopy enables the strict separation of adreno-cortical and adreno-medullary tumors in every case, as tumors of the medulla are generally positive for neuroendocrine markers (chromogranin A, synaptophysin) and negative for D11 whereas those of the cortex are stained with D11 and are negative with the other markers. Our surgical collection of cortical tumors and tumor-like lesions (n = 104) covers adenomas (39%), carcinomas (15%), microadenomatosis (2%), macronodular hyperplasia (4%), hemangioma (1%), myelolipoma (2%), hematoma (1%), pseudocysts (2%), and metastases (6%). The often difficult interpretation of dignity was aided by a point system of criteria. Isolated nodules were differentiated from adenomas by their size (ie less than 3 cm), the histological pattern and the lack of cellular atypia. Correlations of the lesions with the endocrine functions were presented. The tumors of the medulla (n = 42) were differentiated in pheochromocytomas (88%), malignant pheochromocytomas (7%), neuroblastomas (2%), and ganglioneuroblastomas (2%). 8-10% of pheochromocytomas are malignant, but with the exception of invasion of the capsule or of the veins or the demonstration of metastases, no other reliable criteria for malignancy exist. The lack of S100-protein-immunoreacting satellite cells may indicate a malignant growth. 89% of pheochromocytomas in our collection were shown to be endocrine active secreting catecholamines and in one case additionally ACTH.

Adrenal Cortex Neoplasms↗

Carcinomas of the pituitary: definition and review of the literature.

Pituitary carcinomas are defined by their disconnected mode of extension, i.e. by the existence of intra- or extra-cerebral metastases. Since an invasive growth in the sella and its neighboring regions can also be noted in many pituitary adenomas, this invasion cannot be counted as a criterion for malignancy. Almost all pituitary carcinomas stem from previously operated or irradiated invasive adenomas. Like adenomas, they are classified with regard to the presumable cell of origin and the hormone which was produced contingently. Together with 67 pituitary carcinomas already published, three own cases are subject to a critical, summarizing judgement.

Adenoma↗

[Malignant atrophic papulosis].

A 53-year-old woman had noticed numerous papules on her trunk and proximal parts of the limbs. They had healed with a central scar surrounded by a reddish wall. Four months later she had to undergo laparotomy for ileus, resulting from a perforation in the region of the middle jejunum: it was excised and sutured over. At laparotomy white plaque-like lesions were noted on the serosa of both small and large intestine. Histological examination of the jejunal exudate and of a skin biopsy both demonstrated malignant atrophic papulosis (Köhlmeier-Dégos' disease). Treatment with ticlopidine, a platelet-aggregation inhibitor (250 mg twice daily), was initiated and she has now been free of extracutaneous symptoms for 6 years.

Biopsy↗

Combined sellar gangliocytoma and pituitary adenoma in acromegaly or Cushing's disease. A report of 3 cases.

Three cases of a composite sellar tumour composed of a gangliocytoma and an adenoma are presented. Two patients who showed acromegaly and hyperprolactinaemia had a gangliocytoma and a growth hormone (GH)-prolactin cell adenoma in close proximity. The gangliocytoma contained growth hormone-releasing hormone (GHRH) by immunohistochemistry. At the electron microscopical level, the gangliocytoma was characterized by numerous synaptic vesicles. The third patient, a child with Cushing's disease, presented a corticotropin-releasing hormone (CRH)-positive gangliocytoma in close contact with an adrenocorticotropic hormone (ACTH) secreting adenoma, the latter a typical densely granulated ACTH cell adenoma. Ultrastructurally, the gangliocytoma revealed synaptic vesicles and sparse secretory granules. The results suggest that gangliocytomas may promote the development of pituitary adenomas by hypersecretion of releasing hormones. Whereas 20 cases of sellar GHRH producing gangliocytomas in acromegaly are reported in the literature, the combination of a CRH-positive gangliocytoma and an ACTH cell adenoma in Cushing's disease is apparently the first case.

Acromegaly↗

The pathology of the adrenal glands in sudden infant death syndrome (SIDS)

The sudden infant death syndrome (SIDS) is at present based on unknown pathogenetical mechanisms but in industrial nations is the most common cause of death in infancy after the perinatal period. Studies of a large number of adrenal glands in this syndrome have not been reported. Therefore, we evaluated 146 SIDS cases (85 males, 61 females, aged 14-465 days) and 24 control cases (17 males, 7 females, aged 18-623 days) by light microscopy, morphometry and immunocytochemistry (anti-chromogranin A and anti-S100 protein). Our data revealed a normal maturation of the adrenal glands in SIDS cases. Necroses, extensive hemorrhages or inflammation were not found. A focal lipid depletion of the zona fasciculata was seen in 92% of the adrenal glands of the SIDS and control cases. We found a siderosis (in 33% of the SIDS cases and 4% of the control cases) and calcium deposits (13% and 12% respectively) due to hyperemic involution of the fetal zone. The medulla, including the sustentacular cells (S 100 protein-positive cells) and chromaffin cells (chromogranin A-positive cells) was unchanged. Our results indicate that the few morphological alterations of the adrenal glands in SIDS cases are the effect of the underlying disease and not the cause of the sudden death.

Adrenal Cortex↗