Immunological tumour profile: organ-specific carcinoma diagnosis in patients employing the macrophage electrophoretic mobility test.

The macrophage electrophoretic mobility (MEM) test provides a highly sensitive in vitro technique for the detection of cell-mediated immunity in man. The principle involved is the lymphokine-mediated reduction of the negative surface charge of guinea pig macrophages shown by the slowing of the macrophages during cell electrophoresis. Lymphocytes from 162 patients were tested by MEM. They were exposed to a battery of KCl extracts from normal and malignant human tissues, to encephalitogenic protein (EP), to carcinoembryonic antigen (CEA), and to thyroglobulin. Variable lymphocyte responses to EP, CEA and KCl extracts from different cancers gave MEM reaction profiles common to patients with carcinomas of the same organ origin.

Adenocarcinomas of esophagus and cardia in comparison with gastric carcinoma.

Since the carcinomas of the cardia and the adenocarcinomas of the esophagus show many similarities in their histological and morphological descriptions, a detailed comparative study was attempted on the basis of 66 esophageal carcinomas in adenoid differentiation, 359 carcinomas of the cardia, 1288 gastric carcinomas in infracardial localisation, and 492 squamous carcinomas of the esophagus. The evaluation yielded no significant differences between the adenocarcinomas of the esophagus and the cardia neither in age and sex distribution nor with regard to the classifications of Borrmann, WHO, Ming, and Laurén, but a significant discrimination was possible between esophageal and cardial adenocarcinoma together, on the one hand, and infracardial gastric carcinoma on the other. Furthermore, esophageal adenocarcinomas were localized preferentially in the lower third, unlike squamous carcinomas of the same organ. These results suggest that esophageal adenocarcinoma and carcinoma of the cardia must be considered as one separate entity, probably originating from a common stem cell. They further suggest that the cardia belongs to the esophagus rather than to the stomach.

Comparative studies of cardia carcinoma and infracardial gastric carcinoma.

In a part retrospective, part prospective study, 354 carcinomas of the cardia were compared with 1259 infracardial gastric carcinomas with regard to the age and sex of the patients, macroscopic classification, microscopic classifications, depth of invasion, and survival rates. Mortality rates are generally higher in cardia carcinoma than in stomach carcinoma. The difference is due to the significantly poorer survival of cardia carcinoma patients in stage I, while mortality rates in stages II, III, and IV of both types are approximately similar. Highly significant differences were also found with regard to sex ratio, incidence of macro- and microscopic subtypes, and invasive growth. The typical cardia carcinoma occurs preferentially in men, is mostly well-delineated, and is manifested as an ulcerated or polypoid, well-differentiated tumor of expansive growth, corresponding to Laurén's intestinal type. These results confirm the concepts of McPeak and Warren, MacDonald, and Siewert et al., that the carcinoma located in the cardia must be seen as a separate entity of gastric carcinoma.

Association of macrophages detected with monoclonal antibody 25 F 9 with progression and pathobiological classification of gastric carcinoma.

Using monoclonal antibody 25 F 9, which reacts with a determinant of mature macrophages, the inflammatory infiltrate of 66 gastric carcinomas was evaluated using a counting grid. The ratio tumor cells/macrophages was determined for every tumor. For a threshold value of 5, carcinomas with a better prognosis, such as the intestinal type according to Lauré, the expanding type according to Ming and the differentiated carcinomas according to the WHO had a significantly smaller relative content of 25 F 9-positive macrophages (a minimum of P less than 0.05) than the diffuse type, infiltrative type, and undifferentiated carcinomas. Furthermore, the relative macrophage content tended to increase with the stage of carcinomas spread (P less than 0.1). The results suggested that 25 F 9-positive macrophages in gastric carcinoma are of greater significance in tumor spread than in any defensive reaction against the tumor.

Sequence analysis of polymerase chain reaction amplified t(14;18) chromosomal breakpoints in formalin fixed, paraffin wax embedded follicular lymphoma.

AIMS: To determine whether junctional sequences of rearranged chromosomes can be amplified by use of the polymerase chain reaction (PCR) and whether direct sequence analysis of the PCR products is possible, using DNA from formalin fixed, paraffin wax embedded biopsy specimens. METHODS: DNA was extracted from paraffin wax embedded, formalin fixed lymphoma specimens, and junctional sequences of rearranged chromosomes were amplified by the PCR. The products were used as templates for asymmetrical PCR. Subsequently, direct sequence analysis was performed using the chain termination method. RESULTS: Formalin fixed, paraffin wax embedded biopsy specimens and PCR amplification could be used to determine the nucleotide sequences of junctional regions of rearranged chromosomes t(14;18) from patients with follicular lymphoma. CONCLUSION: The identification of junctional sequences of the translocation in follicular lymphoma provides a molecular "fingerprint" of t(14;18) of the lymphoma of an individual patient and can be used for the detection of clone specific DNA in any biopsy tissue obtained from the patient. The strategy used for rapid sequence analysis of PCR amplified DNA sequences will be useful in many areas of molecular pathology.

Immature teratomas of different origin carried by a pregnant mother and her fetus.

We describe the case of a pregnant mother and her fetus who both carried teratomas during the pregnancy. The fetus was diagnosed at 38 weeks' gestation to have an intracranial mass, which was later determined to be an immature teratoma. During a cesarean section delivery, an ovarian tumor was found in the 27-year-old mother that was also diagnosed to be an immature teratoma. Because of the similar histology of the tumors carried by both mother and child, a single clonal origin was suspected. Using polymerase chain reaction (PCR) and electrophoresis of highly polymorphic DNA satellite sequences, we determined that the origin of the intracranial teratoma carried by the child was independent of the mother's tumor. We also examined the p53 tumor suppressor gene in constitutional cells from both mother and child for the possible presence of a cancer-predisposing inherited mutation, but none was found. To our knowledge, this is the first report of the simultaneous occurrence of independent malignant immature teratomas in a mother and child during pregnancy.

Congenital cystic adenomatoid malformation of the lung associated with bile duct hypoplasia.

Congenital cystic adenomatoid malformation (CCAM) is a rare lesion that affects one or two lobes of the lung. Infants are either stillborn or die shortly after birth if therapy is not started immediately. The lesion itself may be solid or cystic, manifesting in an adenomatoid increase in terminal respiratory structures. Clinical, pathological and radiological findings of a child prematurely born are presented. A special feature in this case was hypoplasia of intrahepatic bile ducts, an unusual association with CCAM that has not been previously reported. Pathogenesis and embryological connotations of the two lesions are discussed. The importance of prenatal diagnosis and immediate surgical therapy after birth is stressed.

Demonstration of carcinoembryonic antigen (CEA) by means of the immunoperoxidase technique in paraffin-embedded specimens of tumour tissues.

The unlabelled antibody-enzyme method with the peroxidase-antiperoxidase complex (PAP-complex) was used to demonstrate carcinoembryonic antigen (CEA) or CEA-like substances in paraffin-embedded specimens of tumour tissues with an anti-CEA-antiserum of a rabbit. The anti-CEA-antiserum used in this study exhibited a high anti-CEA-activity and a low activity to an impurity. The paraffin-embedded specimens of tumour tissues were investigated at serum dilutions of 1 : 16, 1 : 64, and 1 : 256. The sections of colorectal cancer showed the highest content of CEA. In 36 of 37 cases the tumour tissue reacted to the anti-CEA-antiserum up to a dilution of 1 : 256. The stomach cancer tissues contained significantly lower CEA-levels than the colorectal cancer. The sarcomas, malignant melanomas, the tumour of testis, the prostatic cancers and basal cell carcinomas of the skin were found to contain none or very low CEA-content. In most specimens of these tumours the CEA was not demonstrable at a 1 : 16 dilution of the primary antiserum.

[Risk of cancer following cholecystectomy, hysterectomy or appendectomy]. / Untersuchungen zum Krebsrisiko nach früherer Cholezystektomie, Hysterektomie oder Appendektomie.

Patients with previous cholecystectomy, hysterectomy or appendectomy have an increased risk of developing cancer of other organs such as the bowel, breast kidney or ovary, particularly if they have undergone more than one operation. Previous nephrectomy, strumectomy, prostatectomy or gastric resection for gastroduodenal ulcer do not increase the risk of bowel cancer.

The value of various methods for determining lymphatic metastases in prostatic carcinoma.

A series of 102 prostatic carcinoma patients was subjected to en bloc pelvic lymphadenectomy. The lymph nodes were collected in groups and examined with the help of the serial section method. An exact N determination is possible by means of the size and location of the lymph node metastases. Compared with this method, the following procedures were critically evaluated: pedal lymphography, excretory urography, clinical examination, explorative lymphadenectomy and pelvic vasography. The results of computer tomography, lymph node biopsy, prostatic lymphography and lymphoscintigraphy are indirectly evaluated. The invasiveness of en bloc lymphadenectomy is discussed.

[Lymphogenic metastases in prostatic cancer--operative and histopathologic investigations ]. / Die lymphogene Metastasierung des Prostatakarzinoms--Operative und histopathologische Untersuchungen.

The necessary application of a differentiated therapy for prostatic cancer requires the involvement of the N-category for determining the therapy. Hitherto existing statements on the lymphogenic metastases of this tumor have been made by means of method whose statements have been limited by the non-presentability of the pelvic lymph nodes, inflammatory-degeneratively changed lymph nodes, and micrometastases. The pelvic en-bloc-lymphadenectomy has been performed and the lymph nodes prepared in successive cuts in the light of a functional patient series of 93 prostatic cancer patients. The standardized procedure allowed statements on the distribution of the pelvic lymph nodes and the corresponding metastases, the size of the metastases and their histologic structure. In prostatic cancer is a high percentage of micrometastases. Lymphogenic metastases can already be detected in low tumor categories, on the other hand metastases are not obligatory in advanced tumors. There is no correlation between the histologic degrees of differentiation of the primary tumor and the lymphogenic metastases. Compared with the metastasis histology the primary tumor histology reveals a distinct morphologic change. According to present investigations, the lymphogenic metastases occur prior to the bone metastases. Since pelvic lymphogenic metastases cannot be covered exactly by means of the conventional methods as well as the metastases cannot be estimated in the single case, there is the necessity for making the pelvic en-bloc-lymphadenectomy before performing a localized tumor treatment such as prostatic vesiculectomy or tele cobalt therapy.

[Hemangioendothelioma--a case contribution]. / Das Hämangioendotheliom--ein kasuistischer Beitrag.

By means of two casuistics the haemangioendothelioma is demonstrated. The malignant tumour may occur in all tissues and organs metastasizing in haematogenic and lymphogenic manners. The thorotrast or vinylchloride-caused promotion of the tumour formation is especially discussed because of its considerably prophylactic importance.

[Isolation of carcinoembryonic antigen]. / Zur Isolierung des karzinoembryonalen Antigens

A method employed in the authors' laboratory for isolating the carcinoembryonic antigen (CEA) from tumours of the entodermal digestive tract and their metastases is described. The main step is fractionation of the preparations obtained by perchloric acid extraction using gel filtration on Sephadex G-200, Sepharose 4 B, and Sepharose 6 B at pH 4.5 and 7.0. The peaks with CEA-specific antigeneity were characterized by the distribution coefficient of the CEA between the mobile and the stationary phases (Kav), and by the relative elution volume (ve/vo). The CEA purified by gel filtration could not reliably be enriched through preparative electrophoresis in Sephadex G-25 gel, polyacrylamide gel or Pevikon powder. The isolation procedures used were compared with those reported in the literature, and the results obtained are discussed.

[Central nervous findings in neurofibromatosis]. / Zentralnervöse Befunde bei Neurofibromatose.

Neurofibromatosis (NF) is subdivided into at least two different forms: NF-1, which is characterized by café-au-lait spots, cutaneous neurofibromas, Lisch nodules and osseous dysplasias, and NF-2, the hallmarks of which are bilateral acoustic neuromas. Neuropathological findings in 5 cases of NF-1 and 3 cases of NF-2 are presented.

[Whipple's disease]. / Ein Beitrag zum Morbus Whipple.

With regard to three cases, one of them relapsing after four years, a short survey on Whipples's disease is given. The 3 male patients of medium age suffered from malabsorption and foregoing arthralgia. These symptoms are typical. In most cases first of all chronic infectious or neoplastic diseases are taken into consideration. The finding of PAS-positive macrophages in biopsies of the duodenal mucosa is key to the diagnosis, allowing the successful antibiotic therapy, with preference to oxytetracyline.

[Fatal complication of a combined coarctation of the aortic arch and isthmus with anomalies of the aortic valve (author's transl)]. / Tödliche Komplikation einer kombinierten Arkus- und Isthmusstenose der Aorta Mit Anomalien der Aortenklappe.

It is reported on a combined coarctation of the aortic arch and isthmus with anomalies of the aortic valve and an aortic sinus aneurysm in case of a 17-year-old woman died of rupture of ascending aorta. By means of histological investigations of aortic tissue taken from aortic coarctation and other areas of aorta it is tried to give a pathognomonic declaration of these anomalies. Findings are allocated to classifications for coarctation of the aorta. Moreover, the pathological findings are subject for comparison with analogous cases mentioned in literature, especially with regard to their frequency, origin, complications, and the age reached.

[Value of lymphography in prostatic cancer - comparison with pelvic en-bloc lymphadenectomy]. / Aussagen der Lymphographie beim Prostatakarzinom - Vergleich mit der pelvinen En-bloc-Lymphadenektomie.

On the basis of 62 pelvic en bloc lymphadenectomies in the carcinoma of the prostate the lymphogenic formation of metastases is histologically determined. In 41 patients the comparison between lymphographic and histological N-determination is performed. The security of the lymphography in the carcinoma of the prostate in the lymphographically establishable pelvic region is recognized with 70%. By the pelvic en bloc lymphadenectomy in 50% of the cases a change of the preoperatively established N-determination takes place. The pedal lymphography is overestimated as method in the carcinoma of the prostate. As a secure technique in the determination of the lymphogenic formation of metastases at present the pelvic en bloc lymphadenomectomy with histological elaboration of the preparations is to be regarded. To this methods belongs a decisive diagnostic evidence in the determination of the formation of metastases of the carcinoma of the prostate by pelvic lymph nodes. The value of the lymphography consists in the simultaneous establishment of aortic metastases. Apart from this an intraoperative X-ray control may partly prove the radicality of the intervention.

p53 protein in benign and malignant sweat gland tumors.

Mutation of the p53 gene and increased levels of p53 protein are among the most frequent alterations in human cancers. To date, very little is known about the mechanisms underlying the development of sweat gland carcinomas. In this study, we analyzed 43 benign and 39 malignant sweat gland tumors for p53 protein level using the antibody PAB1801. Nine (23%) of 39 sweat gland carcinomas were positive for p53 protein. Among these carcinomas, six of 12 cases of extramammary Paget's disease were positive using immunohistochemistry. No other correlation between tumor subtype and p53 reactivity was detected. Among 43 benign sweat gland tumors, only one case displayed staining for p53. We conclude that p53 protein plays a role in a subset of sweat gland tumors, especially in extramammary Paget's disease.

[The significance of pelvic lymph-node status in prostatic cancer]. / Die Bedeutung des Beckenlymphknotenstatus beim Prostatakarzinom.

The formation of metastases of carcinoma of the prostate has become more significant since the introduction of en-bloc pelvic lymphadenectomy using the serial-cut method. Lymphogenous evacuation of the pelvis occurs increasingly with advanced and dedifferentiated primary tumours. However, it can be found with low categories of tumours and differentiated carcinomas. pLA is superior to all other procedures for N-determination. If suitably indicated it allows a localized tumour process to be confirmed. Lymphatic oedemas are the most frequent complications. These can be largely avoided by retention of lacunary lymph nodes or primary fitting of lympho-nodo-venous anastomoses.

Radioimmunological characterization of carcinoembryonic antigen (CEA) preparations.

A multi-step radioimmunological test system was applied to the characterization of carcinoembryonic antigen (CEA) preparations obtained by column chromatography including ion exchange procedure. CEA contents were estimated by means of a sequential inhibition radioimmunoassay using Protein A-bearing Staphylococci for coprecipitation. Data were expressed as "units CEA" and compared with results obtained from commercial CEA-RIA kits. In addition, attempts were made to evaluate the presence of normal cross-reacting antigens in CEA preparations by the application of an antiserum to perchloric acid extract from normal lung tissue. Data from these tests were expressed as "units NLA" (NLA stands for "normal cross-reacting lung antigen"). The factor "units CEA/units NLA" proved useful as an indication of the tumour specificity of those antigenic components measured in the inhibition assay. Moreover, radioimmunoprecipitation tests with subsequent SDS polyacrylamide gel electrophoretic analysis were performed in order to get information on the molecular weight of the molecule(s) involved in the radioimmunological CEA determination procedure. The test system displayed 1) highly specific CEA reagibility in the standard inhibition assay, 2) test sensitivity of about 200 pg CEA (when related to the Hoffman/La Roche test) and 1 ng CEA (when related to CEA-IRE-SORIN), 3) low reagibility to normal cross-reacting antigens, also when compared to the commercial tests, 4) a molecular weight of about 200,000 daltons for the component(s) measured, and 5) evidence of inhomogeneity of the CEA batches investigated and those international references available. The latter might in part be attributed to so-called species-specific CEA-related determinants. The test system proved also useful for CEA estimations in crude tissue extracts.