Ploidy, expression of erbB1, erbB2, P53 and amplification of erbB1, erbB2 and erbB3 in non-small cell lung cancer.

The aim of this study was to assess the prognostic value of deoxyribonucleic acid analysis, expression oferbB1, erbB2 and P53, and amplification levels of erbB1, erbB2 and erbB3 in non-small cell lung cancer (NSCLC). Consecutive patients with NSCLC who underwent treatment with curative intention (118) were included. In 108 cases, the cell cycle was analysed using flow cytometry and double-staining with propidium iodide and anticytokeratin. In another 108 cases, expression of erbB1, erbB2 and P53 was assessed immunhistochemically. Amplification of the erbB family was determined in the tumours of 53 patients using double-differential polymerase chain reaction. Of the tumours, 81% were aneuploid and 14% showed positive staining for erbB1, 18% for erbB2 and 41% for P53. There were normal mean gene copy numbers in 86% for erbB1, 94% for erbB2 and in 96% for erbB3. No significant correlations were noted between erbB1, erbB2 and P53 expression, ploidy status and tumour stage. In a Cox regression model, only tumour stage was shown to be prognostically significant. It seems that ploidy and expression status of erbB1, erbB2 and P53 are not prognostic parameters in non-small cell lung cancer. Amplification of the erbB family does not seem to be a frequent event in non-small cell lung cancer.

Application of computer-assisted morphometry to the analysis of prenatal development of human lung.

Morphometry is well-established in tumour pathology. To evaluate is potential usefulness for description of developmental processes, histological slides from paraffin-embedded specimens of 67 human fetal lungs were Feulgen-stained, and morphometric characteristics of nuclei of epithelial pulmonary cells were analysed with an automated image analysis system. The measured cytometric features comprised of integrated optical density (IOD), S-phase-related IOD fraction, IOD entropy and nuclear area. Histometric features of the specimens were based upon the minimum spanning tree (MST) and included distances between neighboring epithelial cells, between epithelial cells and neighboring lymphocytes, and assessment of MST entropy. Notably, certain parameters revealed a non-uniform level during prenatal development S-phase-related IOD fraction increased from 5% to 8% between 14 and 16 weeks of gestation, then declined to 6% until birth. The IOD entropy steadily increased during development, whereas the extent of nuclear area remained constant. In accordance with an increase of the S-phase-related fraction the MST entropy displayed a singular peak between 14 and 16 weeks of gestation, which is probably associated with development of glandular structures in the lung. Correlation of expression of binding sites for markers, presumably involved in functional aspects of development, with such alterations, is shown for binding capacities of biotinylated fucoidan and the S-phase-related fraction. This may be helpful to infer immuno- or ligando histochemically defined tissue sites with potential physiological significance in morphometrically distinguished periods of development.

[Minimally invasive surgery in persistent pneumothorax and pneumocystis carinii infection]. / Minimal-invasive Chirurgie bei persistierendem Pneumothorax und Pneumocystis-carinii-Infektion.

The most frequent pulmological complication of AIDS is pneumocystis carinii pneumonia (PCP), which in 2% of cases will cause a spontaneous pneumothorax. Every AIDS patient who develops a pneumothorax is highly suspicious for a pneumocystis carinii pneumonia too. We describe the case of an AIDS patient who suffered from pneumothorax caused by PCP. Conventional tube thoracostomy with continuous suction and tetracycline pleurodesis were unsuccessful. The patient recovered however after resection of PCP cysts in the apical upper lobe and talcum pleurodesis by means of minimally invasive surgery.

Primary mucoepidermoid carcinoma of the thymus--a rare cause of mediastinal tumour.

We present a primary mucoepidermoid carcinoma of the thymus which is an extremely rare cause of mediastinal tumour. Growth is slow with cure obtained after complete resection. Only two previous cases have been reported.

[Celiac disease in the adult--a case report]. / Die Zöliakie des Erwachsenen--Ein Fallbericht.

The diagnosis of celiac disease is often missed particularly in cases of adult onset. We report the case of a man in his seventh decade who had been treated for many years for endocrine symptoms and signs of malabsorption. The first biopsy diagnosis of celiac disease was ignored. After a second jejunal biopsy, adequate treatment with a gluten-free diet was initiated. This resulted in recovery. The fact that celiac disease may often present for the first time in adults and that symptoms are not always clear are stressed as well as screening for the disease with the aid of endoscopic techniques.

Expression of cortical and medullary thymic epithelial antigens in thymomas. An immunohistological study of 14 cases including a characterization of the lymphocytic compartment.

Four monoclonal antibodies against antigens expressed differentially by the normal thymus epithelium, which define the cortical, medullary and subcapsular compartments, were used for immunohistological characterization of the epithelial cells in 14 thymomas. Furthermore, thymoma-associated lymphocytes were studied with monoclonal antibodies directed against T-lymphocyte differentiation antigens (CD1a, CD3, T-cell antigen receptor). Only four of the 14 thymomas could be classified into either medullary or cortical type thymoma based on the immunophenotype of epithelial cells. Ten cases escaped immunophenotypical classification due to co-expression of medullary and cortical antigens by the tumour cells. This aberration from the normal phenotype might indicate the failure of differentiation of such tumours. The immunophenotype of the associated lymphocytes, on the other hand, made it possible to classify the tumours as cortical (5 cases), mixed (2) and medullary (3) thymomas. Four thymomas escaped this classification scheme due to the absence of lymphocytes (2) or to a hybrid immunophenotype (2). Nevertheless, thymocytes of cortical type clearly predominated and were seen in all thymomas with associated lymphocytes. This feature may constitute a good diagnostic tool in differential diagnosis since, in 28 mediastinal or extramediastinal metastasis of tumours not derived from thymic epithelium and associated with various numbers of lymphocytes, none of them were found to contain CD1a positive lymphocytes.

[Surgery of lung metastases]. / Chirurgie von Lungenmetastasen.

Between 1975 and 1985 76 patients underwent surgery of pulmonary metastases in our hospital. Most often the primary tumor was located in carcinomas of the colon and rectum (19 patients), followed by carcinomas of the kidney (14 patients), the breast (13 patients) and the skin (malignant melanoma: 9 patients). Conditions for pulmonary metastasectomy are radical removal of the primary tumor, metastases located only in the lung, resectability of the metastases and low operative risk. Three years after pulmonary metastasectomy 35% of the patients were still alive, the 5 year survival rate was 18%. The median survival time was 22 months. The prognosis in patients with pulmonary metastases is largely dependant upon tumor type. Pulmonary metastases of breast carcinomas and carcinomas of colon and rectum can be treated best by surgical intervention. (5 year survival rate: 35% and 33%). Hypernephroma and malignant melanoma have a 5 year survival rate of 0% and 23%. Other prognostic factors are the number of pulmonary metastases and the disease-free interval between surgery of the primary tumor and pulmonary metastasectomy. Furthermore resection techniques are of prognostic importance. Lobectomy and segmental resection showed a better 5 year survival rate than pneumonectomy (21%, 24%, 0%). Median sternotomy is recommended as standard access for pulmonary metastasectomy. Surgery of pulmonary metastases is encouraging.

Stromal composition in bronchogenic carcinomas--morphometric structure analysis.

So far little is known about the pathogenesis and development of the stroma in bronchogenic neoplasia. Clinical and radiological findings and morphological pictures of the tumor taken just after resection, don't reveal information about the pathogenesis and duration of the development of the scar tissue. Using an automatic image analyser (Quantimet 720, Imanco) it was possible to do morphometrical studies of bronchial carcinomas. We correlated the quantity of the stromal reaction in bronchial carcinomas to the size and histological type of the tumor. 60 peripheral, completely excised bronchial tumors were studied using post mortem and surgically removed specimens (25 adenocarcinomas, 22 squamous cell carcinomas, 13 oat cell carcinomas). The mesenchyme was studied histologically and morphometrically at the point of largest circumference of the tumor. Different histological stains were used to identify and correlate epithelial, mesenchymal and necrotic parts of the tumor. Adenocarcinomas on average have 48% stromal composition and even tumors sized 1.5-3 cm2 show evidence of extensive scar tissue. Squamous cell carcinomas have 37% and oat cell carcinomas have 30% fibrous tissue composition. Large adenocarcinomas have less stroma whereas large squamous cell carcinomas showed a relative increase in stromal composition. None of the above was shown in oat cell carcinomas. The amount of stromal tissue therefore depends on the histological tumor type.(ABSTRACT TRUNCATED AT 250 WORDS)

[Volumetric analysis of thyroid lobes by real-time ultrasound (author's transl)]. / Volumetrie der Schilddrüsenlappen mittels Real-time-Sonographie.

Thyroid volume as measured by real-time ultrasound in cadavers was compared with direct measurements obtained by submersion. Length X width X thickness of the thyroid lobe multiplied by factor pi/6, correspond to a rotation ellipsoid, while the best calculated volume of the lobe is obtained by multiplying with the optimised correction factor f = 0.479. The correctness of this calculation is, by definition, 100%; average error of the method is 16%. The measurements are easy to do and require no additional equipment for planimetry or calculations. Volumetric analysis of the thyroid gland is especially necessary in assessing results of treatment and for measuring dosage in connection with radioiodine therapy.

Senile pulmonary amyloidosis.

Lung tissue obtained from 340 necropsies of persons aged 80 years and over was investigated for the occurrence of pulmonary amyloid deposits by means of a sensitive fluorescence technique. The incidence of pulmonary amyloidosis was about 2% below the age of 80, nearly 10% in individuals between 80 and 84 years, and more than 20% at and beyond 85 years. Vascular and concomitant alveolar-septal amyloidosis was seen slightly more often than the pure septal form of senile amyloidoisis. The two modes of deposition correspond to two different forms of cardiac amyloidosis, vascular and nodular. On the other hand, the two different modes of pulmonary amyloidosis affect different age groups. It is postulated that the disorder is related to age-linked immunological disturbances and to genetically determined factors.

Morphometric and cytophotometric investigations of lobular neoplasia of the breast with ductal involvement.

The two different types, A and B, of in situ lobular neoplasia of the breast can be distinguished by cytomorphological means. DNA-measurements of type A are preponderantly diploid while those of type B vary from diploidy to hyperteraploidy with a maximum in the hyperdiploid range. The results indicate a higher potential of malignancy in type B. Homogenous ductular cell proliferations in the immediate neighbourhood of a lobular neoplasia display virtually the same distribution of DNA-values. Such evidence suggests that ductular changes and concomitant intralobular lesions have a common genesis, showing also a similar tendency towards malignant changes.

Cytophotometric DNA-measurements in abortion.

Triploid abortuses ascertained by cytogenetic analysis histologically show molar degeneration of the placental villi. Changes of this type which are occasionally encountered in routine material may suggest chromosome abnormality although chromosome analysis is precluded due to fixation. However, suspected triploidy can be proven in Feulgen-stained sections by DNA-measurements. In nine cases of molar degeneration selected according to histological criteria, evaluation of nuclear DNA-content revealed only two triploid placentae. It seems acceptable to assume that such molar changes in diploid abortuses may be due to prolonged retention of the placenta. Thus, histological criteria may suggest but cannot establish the diagnosis of triploidy. In case of susepcted triploidy of the feto-placental tissue, DNA-measurements can confirm or exclude the diagnosis even if a cytogenetical analysis is not applicable.

The nuclear DNA content of lobular neoplasia of the mammary gland.

Twelve cases of lobular neoplasia and three cases of invasive lobular carcinoma of the breast were examined by Feulgen microspectrophotometry. Two different ranges of nuclear DNA values were observed. Eight cases of lobular neoplasia fell within the diploid range and the four remaining cases within the diploid to tetraploid range, while the three cases of invasive lobular carcinoma showed a DNA distribution between the diploid and tetraploid range. Cytophotometrically, lobular neoplasia with diploid DNA values can be considered to represent a precancerous condition, whereas lobular neoplasia with diploid to tetraploid values are regarded as a more advanced stage of an non infiltrating carcinoma still confined to the performed spaces.

[Cystinosis, hyperparathyroidism and metastatic calcifications (author's transl)]. / Nephropathische Cystinose, Hyperparathyreoidismus und Kalkmetastasen

An 11-year-old boy died from uraemia in the course of cystinosis. In addition to the renal lesions common to this disease he had also developed nodular hyperplasia of the parathyroids and widespread extra-osseous calcifications in lungs, kidneys, stomach, the muscular arteries, skin and subcutaneous tissue. The calcifications and other features suggest that the hyperparathyroidism was a "tertiary" one, although this term is not generally accepted. The unusual cutaneous calcifications were probably due to calciphylaxis. As in this case, hyperparathyroidism and calcinosis can develop into a "second disease" which, due to the cystinosis, may follow a remarkably autonomous course.