[Urine examination for tumor cells using quantitative immunocytochemistry. Antibodies to a CEA-like antigen]. / Urinuntersuchungen auf Tumorzellen mittels quantitativer Immunzytochemie. Antikörper gegen ein CEA-ähnliches 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.

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.

Effects of octreotide on morphology of pituitary adenomas in acromegaly.

We studied the effects of the long-acting somatostatin analogue octreotide (SMS 201-995, Sandoz, Basel, Switzerland) on the morphology of pituitary adenomas in acromegaly. Of the 29 adenomas examined by light microscopy, 16 had been treated pre-operatively with octreotide. The treated adenomas were compared with the untreated adenomas. 14 adenomas were also studied by electron microscopy. In 23 cases we performed in-situ-hybridization for GH-mRNA. Under light microscopy, we found a decrease in amyloid deposits and a higher amount of cell necroses and fibroses after treatment, mainly in the tumors with shrinkage. Tumor shrinkage was diagnosed when the maximal diameter of the adenoma decreased for at least 1/3 during octreotide treatment in NMR examination. Immunohistochemical examinations showed that treated adenomas, especially those with tumor shrinkage, possessed more GH immunoreactive cells, and after in-situ-hybridization we found a higher content of GH-mRNA. On the ultrastructural level, rough endoplasmic reticulum appeared to be increased in treated adenomas. The increase of GH-mRNA and of rough endoplasmic reticulum suggests the likelihood of an increased secretory activity due to a rebound effect after short-term pre-operative omission of octreotide. Other findings are discussed.

Demonstration of pro-opiomelanocortin mRNA in pituitary adenomas and para-adenomatous gland in Cushing's disease and Nelson's syndrome.

Pro-opiomelanocortin (POMC) mRNA was demonstrated in pituitary adenomas from 16 patients with Cushing's disease and 10 with Nelson's syndrome. The intensity of signal was significantly greater in Nelson's syndrome than in Cushing's disease and there was a trend towards a greater proportion of positive cells. This probably reflects inhibition of POMC gene expression by the high circulating levels of cortisol in Cushing's disease. In the para-adenomatous gland, the intensity of signal was variable in cells showing Crooke's hyaline change, ranging from negative to strongly positive, in keeping with the functional heterogeneity of corticotrophs. In one case, junctional corticotrophs were present and these were more intensely stained than anterior lobe corticotrophs in the same gland. This supports the concept that these cells are subject to different regulatory influences from corticotrophs in the anterior lobe. Whether this is related to differences in embryological origins or to local factors is at present unclear.

Tumors of the sellar region mimicking pituitary adenomas.

In the sellar region most tumors of our collection (n = 1937) are pituitary adenomas, followed by craniopharyngiomas, chordomas and meningiomas. Difficulties in morphological differential diagnosis by light microscopy may occur in meningiomas, plasmacytomas, chordomas and germinomas. In these cases, immunohistological investigations and sometimes even electron microscopy are helpful in solving the problems. Meningiomas can sometimes resemble pituitary adenomas. Of diagnostic value in these cases is the expression of vimentin and S-100-protein in the meningioma cells. Plasmacytomas may also mimic pituitary adenomas. In these cases, the positive reaction with antibodies against LCA and immunoglobulins or against kappa-light-chains and lambda-light-chains leads to the diagnosis. Chordomas, too, can sometimes be hardly distinguished from pituitary adenomas. In these cases, the expression of S-100-protein, vimentin and CEA by the chordoma cells and the typical electron microscopic features of chordomas are helpful for the differential diagnosis. Germinomas may sometimes be indistinguishable from lymphocytic hypophysitis. Of diagnostic importance are here the expression of HCG and placental alkaline phosphatase by germinoma cells. In the above mentioned cases, it is also important to perform immunohistochemical examinations for pituitary hormones including alpha-subunit. All these tumors do not express these hormones.

Invasiveness of pituitary adenomas.

528 biopsies from 396 pituitary adenomas were re-examined by light microscopy and checked for invasion of neighbouring tissues. The overall invasion rate was 41.9%. Highly differentiated ACTH-cell adenomas were invasive in 24.1%, undifferentiated mucoid-cell adenomas in 66.7%. The histological type of invasion was influenced by the adenoma type and by the invaded tissue. There was no obvious correlation between the adenoma type and the invaded tissue.

Induction of globin mRNA accumulation by hemin in cultured erythroleukemic cells.

The role of heme in erythroid development is investigated in erythroleukemic (Friend) cells. Exogenous hemin induces the accumulation of globin mRNA and globin protein in T3-C12 erythroleukemia cells to levels comparable to those induced by polar solvents, such as dimethylsulfoxide (DMSO). The hemin concentration required for maximal induction (10(-4) M) is the same as that which stimulates globin message translation in reticulocytes or cell-free reticulocyte lysates. Hemin and DMSO together cause T3-C12 cells to accumulate 8-9 fold more globin mRNA than either inducer individually. The kinetics of globin mRNA induction in hemin as compared to DMSO are very different: globin message accumulation begins 4 hr after hemin addition, but not until 30--40 hr after DMSO addition. Biliverdin induces 20--40 fold less hemoglobin than hemin; delta-aminolevulinic acid and porphobilinogen do not induce.