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W Saeger

Publications and source records attributed to W Saeger.

At least 19 recordsLinked to original sources

[Amyloid: microscopic demonstration, classification and clinical correlation].

Amyloid is a biophysically defined, biochemically non-uniform protein which is deposited in the tissue, forming a cross-beta configuration. In paraffin sections it is demonstrated using Congo red staining according to Puchtler et al. and a polarizing microscope with a tension-free clean optic system that shows a typical apple-green birefringence. The identification of amyloid has to be followed by immunostaining for AA, ATTR, A lambda, A kappa and A beta 2 microglobulin and possibly further types of amyloids for classification purposes. Considering the localization, expansion and type localized and generalized types probably can be differentiated. The latter should be correlated to a basic disease. The treatment of the basic disease is the only chance for reducing or eliminating the amyloid deposits. In this review, the modern morphological methods for demonstration and both immunohistological and clinical classification of amyloid and amyloidoses are presented. Rare types are mentioned in the tables.

Amyloid

Diagnosis and immunohistochemical classification of systemic amyloidoses. Report of 43 cases in an unselected autopsy series.

Fourty-three cases of systemic amyloidosis were identified in an unselected autopsy series from our institute (6305 autopsies between 1979 and 1993) and classified immunohistochemically by means of a panel of antisera directed against five major amyloid fibril proteins. Amyloid A (AA) amyloidosis was the most common type, being found in 21 cases (48.8%). Transthyretin-derived (ATTR) amyloidosis was present in 11 cases (25.6%), and immunoglobulin light chain-derived (AL) amyloidosis in 10 cases (23.3%). A single case (2.3%) contained deposits of more than one type of systemic amyloid. AA amyloidosis was associated with chronic inflammatory or infectious diseases (81%), malignant tumours (19%) or both (9.5%). Immunoglobulin light chain-derived amyloidoses were associated with myeloma (50%) or primary (idiopathic; 50%). In AA and AL amyloidosis the kidney was the organ most frequently involved. ATTR amyloid affecting mostly the heart and lungs presented as senile systemic amyloidosis. Systemic amyloidosis was the cause of death in 5 cases (12%) and caused symptoms in 17 cases (39%). Our results suggest that most cases can be classified by using a panel of sensitive and specific antibodies against five major amyloid fibril proteins. This technique may make amyloid type-specific therapy possible for AL amyloid patients who do not have evidence of an underlying plasma cell dyscrasia.

Aged

Basement membrane proteins, apolipoprotein E and glycosaminoglycans in pituitary adenomas and their correlation to amyloid.

The aim of the study was to confirm earlier reports of the association of amyloid deposits in growth hormone (GH)-producing adenomas of the pituitary and the presence of glycosaminoglycans, basement membrane proteins and apolipoprotein E (apo E). Serial sections from 17 amyloidotic and 11 nonamyloidotic, sparsely granulated, GH-producing adenomas obtained from patients presenting with acromegaly were stained with Congo red and Alcian blue, and also with antisera directed against fibronectin, collagen IV, laminin and apo E. Glycosaminoglycans were found in capillaries of every adenoma and were also related spatially to amyloid deposits. Immunostaining of both nonamyloidotic and amyloidotic adenomas demonstrated the presence of fibronectin, collagen IV and laminin in the basement membranes of surrounding nonadenomatous tissue and tumour vessels. In approximately half the amyloidotic adenomas, each basement membrane protein presented with a distinct spatial relationship to amyloid deposits. Apo E was found in 88% of the amyloidotic adenomas within the amyloid deposits, and in six cases intracellular immunostaining was also evident in folliculo-stellate cells. The results are consistent with the presence of glycosaminoglycans, basement membrane proteins and apo E in the amyloid deposits of pituitary adenomas.

Adenoma

Clinically nonsecreting pituitary adenomas in childhood and adolescence.

OBJECTIVE AND PATIENTS: Clinically nonsecreting pituitary adenomas are rare in childhood and adolescence. We analyzed five cases of clinically nonsecreting pituitary adenomas in patients (4 male and 1 female patient) under 20 years of age at surgery (0.22%), identified by a review of 2288 patients with pituitary adenomas treated from 1970 to 1996 at the Hamburg University. CLINICAL PRESENTATION AND RESULTS: Patient age at the onset of symptoms ranged from 8 to 13 years (mean, 10.8 yr), and age at surgery ranged from 12.5 to 19.5 years (mean, 15.5 yr). Two patients presented with endocrine symptoms, two with headache only, and one with a visual field defect. Endocrinological examinations showed pituitary insufficiency in two patients with endocrine symptoms. The serum prolactin level was normal in all patients. Radiological investigations demonstrated resectable macroadenomas with ring enhancement in four patients and a nonresectable macroadenoma with parasellar extension in one. Transnasal explorations achieved radical tumor resection except in one patient. The latter underwent a transcranial resection and radiotherapy because of parasellar tumor rest. Surgical morbidity consisted of left oculomotor nerve palsy after transcranial exploration. In two patients, normal pituitary function was preserved by transnasal surgery. Follow-up duration was 2 to 23 years (mean, 10.9 yr). There was no recurrence except for one parasellar adenoma. Immunohistological diagnosis was null cell adenoma in two patients, silent prolactinoma in two, and silent gonadotroph adenoma in one. The proliferative activity measured by Ki-67 (as the antibody MIB-1) and p53 expression revealed a positive reaction in one adenoma with parasellar extension. CONCLUSION: Clinically nonsecreting pituitary adenomas in childhood and adolescence cause different endocrine symptoms from those in adults. They caused pubertal and growth delay and/or primary amenorrhea in the patients investigated in this study. Transnasal surgery in childhood and adolescence is as safe as in adults. The characteristics of nonsecreting pituitary adenomas in this age group, including 20 patients cited from the literature, do not differ from those in adults.

Adenoma

[Combined neuronal and endocrine tumors of the sellar region].

Gangliocytomas or gangliogliomas of the sellar region are very rare tumors. In a great proportion of those cases an adenoma of the anterior pituitary develops from the cell type that is hyperstimulated by the releasing hormone produced from the gangliocytoma. Five GHRH secreting gangliocytomas are reported. Four of these were localized adjacent to a GH secreting adenoma. In one case, no adenoma tissue was found beside the ganglicytoma. As only the adenomas can secrete GH, the adenomas and not the gangliocytomas are directly responsible for acromegaly so that such an adenoma has to be present in cases of acromegaly. A CRH secreting gangliocytoma was combined with an ACTH cell adenoma that had induced Cushing's disease. A ganglioglioma of the posterior pituitary had led to an inappropriate secretion of Vasopressin. The morphology of the different tumors is presented.

Acromegaly

Morphology, immunohistochemistry and morphometry of pancreatic islets in cases of sudden infant death syndrome (SIDS).

The pancreatic islets from 112 infants (66 males and 46 females) who died of SIDS during the years 1990-1992 have been studied. The control group consisted of endocrine pancreas tissue from 19 infants who died of a clear cause of death (pneumonia, drowning, sepsis, etc.). The mean age of the SIDS group was 5.1 months. We found histologically normally developed organs in all the SIDS cases. By evaluating the relative endocrine cell area of the pancreas by immunohistochemical investigations, A-cells were found to make up 10-30%, B-cells 30-60%, D-cells 10-30% and pancreatic polypeptide cells less than 10% in the SIDS group and in the controls with a small increase in glucagon and insulin cells among SIDS cases. The morphometric evaluation revealed that cell enlargement and cytoplasm shrinking occurred slightly more often in the SIDS group than in the control group. The diameter of the islets was normal and the maximal volume was not enlarged. The results did not show significant differences so that a relationship between alterations of the endocrine pancreas and sudden infant death syndrome could not be demonstrated.

Cell Size

Results of somatostatin receptor scintigraphy do not predict pituitary tumor volume- and hormone-response to ocreotide therapy and do not correlate with tumor histology.

The value of somatostatin receptor scintigraphy (SRS) to predict the effect of somatostatin analog therapy on pituitary adenomas is not clear, due to the use of different radiopharmaceuticals (123I-Tyr3-octreotide and 111In-pentetreotide) and the small number of patients in previous studies. We used 111In-pentetreotide scintigraphy in 49 patients in order to (i) correlate SRS results with basal tumor volume as well as volume- and hormone-response to 3 months of octreotide therapy (Oct-Tx). (ii) identify tumor remnants after incomplete surgery and (iii) evaluate any correlation with immuno histology. Twenty-five patients had a GH-secreting adenoma (GH-A, 15 prior to intended surgery, 10 with persistent/recurrent disease after previous therapy). Twenty-four patients had a clinically non-functioning adenoma (NF-A). For SRS, planar and single photon emission computer tomographic images (SPECT) were recorded 4 h and 24 h post injection. SRS grading was as follows: GO, no uptake: G1, uptake comparable to normal pituitary; G2, increased uptake: G3, very intense uptake. G2/3 was seen in 8/25 GH-A and in 12/24 NF-A. Pretreatment tumor volume (magnetic resonance imaging (MRI) tended to be related to 111In-pentetreotide uptake in GH-A with a tumor visible on MRI (G0/1 (n = 10) vs G2/3 (n = 8): 3.6 +/- 1.9 vs 10.5 +/- 6.5 cm3 (mean +/- S.E.), P = 0.051), but not in NF-A (G0/1 (n = 12) vs G2/3 (n = 12): 17.0 +/- 10.1 vs 14.3 +/- 3.6 cm3). SRS did not identify a tumor remnant in the 7 MRI-negative patients with persistent post-operative acromegaly. Basal GH (6-h profile) and IGF-1 in GH-A did not correlate with SRS results (G0/1 (n = 17) vs G2/3 (n = 8), GH: 32.3 +/- 18.2 vs 29.3 +/- 7.4 micrograms/l IGF-I: 851 +/- 80 vs 1038 +/- 153 micrograms/l). During Oct-Tx of GH-A neither tumor shrinkage nor GH suppression was related to SRS results. In 6 NF-A classified as gonadotropinomas (by their plasma glycoprotein hormone or alpha-subunit concentrations, basally and/or in response to TRH) 111In-pentetreotide uptake was not different from that of the non-gonadotropin/non-secreting adenomas. SRS results were not related to the immunohistological subtype in 22 GH-A (monohormonal mixed somatotrope/lactotrope, plurihormonal) or in 22 NF-A (null-cell adenomas, gonadotropinomas silent hormonal adenomas). We conclude that 111In-pentetreotide SRS reflects tumor volume poorly in GH-A and not at all in NF-A. It does not predict the effect of Oct-Tx on the volume of both GH-A and NF-A, nor on the GH concentration in GH-A. 111In-pentetreotide SRS is unable to identify post-operative tumor remnants not visible on MRI.

Adenoma

Occult eutopic Cushing's syndrome--failure of simultaneous bilateral petrosal sinus sampling to diagnose pituitary-dependent Cushing's syndrome.

Simultaneous bilateral inferior petrosal sinus (IPS) sampling has been repeatedly proposed to be a highly specific approach for the diagnosis of Cushing's disease and 100% sensitivity in detecting autonomous pituitary ACTH secretion by an adenoma has been reported in a large series. We now report on a patient suffering from ACTH-dependent Cushing's syndrome in whom repeated bilateral IPS sampling failed to detect a central/peripheral gradient diagnostic for autonomous pituitary ACTH secretion during initial evaluation. Applying lysine vasopressin as the corticotroph secretatogue, the maximum central/peripheral gradient was 1.0 before and 1.1 following stimulation. Moreover, results of high dose dexamethasone and corticotrophin releasing hormone administration suggested ectopic ACTH secretion. Since thorough diagnostic procedures failed to localise a suspected carcinoid tumour, occult ectopic Cushing's syndrome was diagnosed. Eight years later, a pituitary macroadenoma was detected by magnetic resonance imaging (MRI), IPS catheterisation then revealed a maximal central/ peripheral gradient of 9.3 before and 20.4 after the intravenous administration of lysine vasopressin. Resected tumour tissue was classified as a typical densely granulated ACTH cell adenoma. We conclude that repeated MRI scans should be included in the follow-up of patients with a diagnosis of occult ectopic Cushing's syndrome to avoid the risk of overlooking 'occult eutopic Cushing's syndrome'.

Adenoma

Current pathological classification of pituitary adenomas.

A classification of pituitary adenomas basing on detailed structural and immunohistochemical studies is accepted world-wide and is mandatory for each pathologist. Monohormonal (densely or sparsely granulated GH cell adenomas, Prolactin cell adenomas, ACTH cell adenomas. FSH/LH cell adenomas, alpha-subunit-only adenomas), bihormonal (mixed GH/Prolactin cell adenomas, mammosomatotroph cell adenomas, acidophil stem cell adenomas), plurihormonal (GH/Prolactin/Glycoprotein-positive adenomas, other Glycoprotein-positive types) and hormone-negative adenomas (null cell adenomas, oncocytic adenomas) have to be differentiated.

Adenoma

Senile amyloidoses of the pituitary and adrenal glands. Morphological and statistical investigations.

The pituitary and adrenal glands are a functional endocrine unit affected by local or organ-limited senile amyloid syndromes. These occur as interstitial (pituitary only) or intracellular (pituitary and adrenal) varieties. The pituitary and right adrenal glands of each of 108 consecutive autopsy cases of individuals aged 85 years and over were investigated for the prevalence, distribution and immunostaining characteristics of local amyloid. Intracellular amyloid was detected in 77 (71%) pituitaries and 73 (68%) adrenals. Interstitial amyloid was found in 86 pituitaries (80%). Immunohistochemical studies, investigating different amyloid fibril proteins, amyloid P component, ubiquitin, intermediate filaments and pituitary hormones, failed to demonstrate any similarities, and a common origin is unlikely. Statistical analyses demonstrated significant correlations between the occurrences of all three local amyloids. The clinical and histopathological significance of local pituitary and adrenal amyloid remains obscure. The results suggested that the pathogenesis of the local senile amyloidoses of the pituitary and adrenals may be influenced by a common, still uncharacterized variable. It is not clear whether this variable also contributes to the pathogenesis of other senile amyloid syndromes, such as those associated with Alzheimers' disease.

Adrenal Glands

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

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