Immunohistological detection of estrogen and progesterone receptors in multiple and well differentiated leiomyomatous lung tumors in women with uterine leiomyomas (so-called benign metastasizing leiomyomas). A report on 5 cases.

Seventy-four cases of so-called "benign metastasizing uterine leiomyomata" are reported in the literature. In these cases, well differentiated, leiomyomatous lung tumors developed, usually after a period of several years. Histologically, these tumors appear to be benign. We report on five more such cases in which we investigated the contents of estrogen and progesterone receptors in the pulmonary tumors by immunohistological procedures. All the lung tumors exhibited a high content of progesterone receptors, and in 4 out of the 5 cases a high estrogen receptor content was also found. Modern immunohistological techniques permit the investigation of routinely fixed tissue blocks, and it is thus recommended that the contents of these hormone receptors should be determined in well differentiated, leiomyomatous lung tumors from women. This would both provide information on the pathogenesis of these tumors and establish a basis for possible later institution of hormone treatment. It is likely that the majority of these lung tumors are in fact metastases of extremely well differentiated leiomyosarcomas of the uterus. The possibility that lung tumors of this type may constitute a small group that develop in situ as hormone-sensitive proliferations cannot, however, be fully excluded.

Extracerebral toxoplasmosis in AIDS. Histological and immunohistological findings based on 80 autopsy cases.

Despite the great amount of literature concerning toxoplasmic encephalitis in AIDS patients, little is known about extracerebral toxoplasmosis. Therefore we conducted a study of 80 autopsy cases to estimate the frequency of extracerebral toxoplasmosis. A control group of 50 cases was completely negative for all markers applied. In 35 of the 80 AIDS-cases (43.7%), organisms could be detected. In 13 cases (16.2%) there was an extracerebral toxoplasmosis; 4 cases (5%) showed only extracerebral involvement and in 9 cases (11.2%), extracerebral toxoplasmosis occurred in combination with cerebral manifestations. In 22 cases (27.5%), only cerebral toxoplasmosis was found. The following organs were involved: cardiac muscle (15%), lungs (6.2%), liver (5%), pancreas (5%), gastrointestinal tract (6.2%), adrenal glands (5%), lymph nodes (5%) and testis (3.7%). In individual cases further organs, not mentioned above, were involved. Pseudocysts could be demonstrated within necroses and inflammatory foci by conventional staining, whereas trophozoites became apparent only immunohistologically.

Subcutaneous granuloma annulare of the eyelid. A case report.

A rare case of subcutaneous granuloma annulare of the eyelid is reported. A diabetic patient developed a unilateral periorbital tumorous mass. Biopsy revealed subcutaneous palisading granuloma. By microscopy and immunohistology, other granulomatous reactions including necrobiosis lipoidica could be ruled out. Since treatment with dapsone was without effect, the tumor was surgically excised. The differential diagnosis and the literature are briefly discussed.

[Pathogenicity of Acanthamoeba isolated from water]. / Versuche über die Pathogenität von aus Gewässern isolierten Acanthamöben.

Two Acanthamoeba strains were isolated from rivers in Berlin by intranasal inoculation into mice. No clinical or pathological symptoms could be observed in the animals. The intention of this study was to initiate and to increase the pathogenicity of these amoebae. The two strains were passaged in mice as well as in liquid medium followed by inoculation into mice. The pathogenicity was measured by the rate of lethality. The first cases of death were found after the 10th passage in those mice which had been infected with the amoebae only passaged in animals. Acanthamoebae could be isolated from brains and lungs, but pathological changes were found only in lungs. After the 11th and 12th animal passage, respectively, the amoebae were only cultivated in vitro for 15 weeks followed by another series of animal passages. Here, first cases of death were recorded after the 5th and 3rd inoculation into mice, respectively. No animals died having been infected with amoebae only maintained in vitro. A third experiment with animal passaged strains showed that mice died even up to the 6th week p.i. and that amoebae could be re-isolated until the 7th week i.p. The results are discussed in view of a possible selection of pathogenic Acanthamoeba strains by fast passages from man to man.

Origin and evolution of primate social organisation: a reconstruction.

The evolution and origin of primate social organisation has attracted the attention of many researchers, and a solitary pattern, believed to be present in most nocturnal prosimians, has been generally considered as the most primitive system. Nocturnal prosimians are in fact mostly seen alone during their nightly activities and therefore termed 'solitary foragers', but that does not mean that they are not social. Moreover, designating their social organisation as 'solitary', implies that their way of life is uniform in all species. It has, however, emerged over the last decades that all of them exhibit not only some kind of social network but also that those networks differ among species. There is a need to classify these social networks in the same manner as with group-living (gregarious) animals if we wish to link up the different forms of primate social organisation with ecological, morphological or phylogenetic variables. In this review, we establish a basic classification based on spatial relations and sociality in order to describe and cope properly with the social organisation patterns of the different species of nocturnal prosimians and other mammals that do not forage in cohesive groups. In attempting to trace the ancestral pattern of primate social organisation, the Malagasy mouse and dwarf lemurs and the Afro-Asian bushbabies and lorises are of special interest because they are thought to approach the ancestral conditions most closely. These species have generally been believed to exhibit a dispersed harem system as their pattern of social organisation ('dispersed' means that individuals forage solitarily but exhibit a social network). Therefore, the ancestral pattern of primate social organisation was inferred to be a dispersed harem. In fact, new field data on cheirogaleids combined with a review of patterns of social organisation in strepsirhines (lemurs, bushbabies and lorises) revealed that they exhibit either dispersed multi-male systems or dispersed monogamy rather than a dispersed harem system. Therefore, the concept of a dispersed harem system as the ancestral condition of primate social organisation can no longer be supported. In combination with data on social organisation patterns in 'primitive' placentals and marsupials, and in monotremes, it is in fact most probable that promiscuity is the ancestral pattern for mammalian social organisation. Subsequently, a dispersed multi-male system derived from promiscuity should be regarded as the ancestral condition for primates. We further suggest that the gregarious patterns of social organisation in Aotus and Avahi, and the dispersed form in Tarsius evolved from the gregarious patterns of diurnal primates rather than from the dispersed nocturnal type. It is consequently proposed that, in addition to Aotus and Tarsius, Avahi is also secondarily nocturnal.

[Combined cytostatic chemotherapy of advanced non-small-cell bronchial carcinoma with doxorubicin and ifosfamide]. / Kombinierte zytostatische Chemotherapie des fortgeschrittenen nicht-kleinzelligen Bronchialkarzinoms mit Doxorubicin und Ifosfamid.

Fifty-three patients with inoperable non-small cell bronchial carcinoma were treated at four-weekly intervals with two cytostatic drugs, doxorubicin (50 mg/m2 on day 1) and ifosfamide (2000 mg/m2 on days 1-3). To avoid urotoxicity of ifosfamide, mesna, a uroprotective drug, was additionally given intravenously at a dose of three times 400 mg/m2 on days 1-3. All diagnoses had been histologically and/or cytologically confirmed. Adenocarcinoma was present in 22, large-cell undifferentiated carcinoma in 18, and squamous-cell carcinoma in 13. Distant metastases were present in 46, seven had a regionally localized tumour growth. There were one complete and 20 partial remissions (response rate 40%). Among a further 19 patients temporary growth arrest was registered. The remissions occurred in seven with adenocarcinoma, nine with large-cell carcinoma and five with squamous-cell carcinoma. Median remission was 8.3 months, mean survival time 10.5 months. Patients without response survived a mean of 5.5 months, patients with tumour progression for 1.3 months (Kaplan-Meier method). Most prominent among side-effects were cardiotoxicity and infection during the leukopenic phase. Urotoxicity was minor, due to treatment with mesna. The results suggest that doxorubicin and ifosfamide in combination can be considered an effective means, with acceptable toxicity, of treating advanced non-small cell bronchial carcinoma.

Evidence of cross-reactivity of 'carcinoma-specific' KC4 monoclonal antibody with activated mesothelial cells and phytohemagglutinin-stimulated lymphocytes.

Carcinoma-specific antibodies would be a useful tool in immunocytology of serous effusions. We tested the carcinoma-'specific' monoclonal antibody KC4 with cells obtained from pleural effusions evaluated by thoracoscopy and pleural biopsies. KC4 reacted most strongly with carcinoma cells. However, activated mesothelial cells also expressed this marker strongly. Lymphocytes stimulated with phytohemagglutinin were also stained by KC4. Thus KC4 appears to detect a proliferation antigen rather than a carcinoma-specific antigen.

Fungal infections following heart transplantation.

Following heart transplantation (HTx), patients often suffer from mycoses due to the necessary immunosuppressive treatment to prevent rejection episodes. Oropharyngeal Candida infections which mostly occur after HTx under high-dose immunosuppressive therapy can be avoided and treated successfully by prophylactic medication to be started immediately after transplantation, either by using azoles (e.g. fluconazole) or amphotericin B suspension. Contrary to this, invasive aspergillosis, beginning in the upper respiratory tract and the lung and mostly followed by hematogenous dissemination into various organs, is always a serious disease with high mortality. To avoid this infection, specimens from the respiratory tract, serum and urine should be examined mycologically prior to HTx. After HTx, apart from prophylactic avoidance of exposure to airborne fungal spores, close mycological control is mandatory to detect colonizations by aspergilli early. Timely administration of amphotericin B and 5-flucytosine, i.e. as soon as invasive growth is suspected, enables curative treatment of the often lethal course of this disease, even under immunosuppressive therapy.

[Prospective comparison of the diagnostic value of cytology and immunocytology in pleural effusion studied by thoracoscopy and biopsy]. / Prospektiver Vergleich der diagnostischen Wertigkeit von Zytologie und Immunzytologie bei thorakoskopisch-bioptisch untersuchten Pleuraergüssen.

Two issues have been elaborated: the value of immunocytochemistry in the diagnosis of pleural effusions, and the reactivity of the investigated antibodies with different classes of cells in pleural effusions. Effusions of unknown origin from 38 patients were investigated using thoracoscopy, pleural biopsies, conventional cytology, and immunocytochemistry. The following antibodies were used: those monoclonal against various leukocyte antigens, macrophage antigens, epithelial membrane antigen (EMA), various cytoskeleton antigens, and melanoma antigens; those polyclonal against CEA and ferritin. All of the techniques used showed 18 patients (48%) as having a tumor-cell negative effusion. A pleural tumor with a malignant effusion showed in 13 patients (34%); in 12 of these immunocytochemistry also revealed tumor cells. Seven patients (18%) had a tumor of the pleura with a tumor-cell negative effusion; in 2 of these immunocytochemistry revealed a tumor-cell positive effusion. There was no difference with regard to the number of NK cells in patients with inflammation of the pleura and negative cytology and patients with tumor of the pleura and malignant effusion (3% vs 4.5%). Tumor cells were mainly stained by EMA, cytokeratin, and CEA. CEA was the only antibody to be tumor-cell specific, while EMA and cytokeratin were expressed by mesothelial cells also. The antibody against ferritin was a significant marker for mesothelial cells.

Liver graft-transmitted glioblastoma multiforme. A case report and experience with 13 multiorgan donors suffering from primary cerebral neoplasia.

The transmission of donor-related malignancies by organ transplantation is a rather rare event. There has only been one report on the development of a brain tumor metastasis in liver transplantation. From September 1988 to January 1993, 342 donor hepatectomies with subsequent transplantation were performed at our center. The main donor diagnoses included subarachnoidal bleeding (n = 128; 37.4%), isolated head injury (n = 114; 33.3%), multiple injuries (n = 55; 16.1%), primary cerebral neoplasia (n = 13; 3.8%), and other (n = 32; 9.4%). Primary cerebral neoplasia included glioblastoma (n = 4), meningioma (n = 3), astrocytoma (n = 2), angioma (n = 2), neurocytoma (n = 1), and ependymoma (n = 1). In the group of donors suffering from primary cerebral neoplasia, procured organs other than the liver included kidneys (n = 20), combined kidneys and pancreata (n = 1), pancreata (n = 2), hearts (n = 8), combined hearts and lungs (n = 1), and single lungs (n = 1). Follow-up of the respective graft recipients ranged from 28 to 68 months (median 43 months). Recurrent malignancy was observed once, in a liver graft recipient. The donor, a 48-year-old female, had undergone surgical resection of an intracerebral multiform glioblastoma and died 4 months later of a relapse in the brain stem. The 28-year-old female recipient had undergone transplantation for an autoimmune-hepatitic cirrhosis. Four months later, histopathological examination of an intraperitoneal and intrahepatic mass revealed a poorly differentiated, small-cell pleomorphic cancer, identified as a glioma metastasis by S100- and glial fibrillary acidic protein immunohistochemical staining. The patient died 6 months post-transplantation. On autopsy, no further neoplastic lesions were detected. Our review adds a second reported case of a liver graft-transmitted brain tumor to the literature and the fourth donor-related malignancy after hepatic transplantation in general.

Histological findings after transmyocardial laser revascularization.

In recent time, it has become more and more probable that patients with severe diffuse coronary artery disease, who are not candidates for aortocoronary bypass surgery or percutaneous transluminal coronary angioplasty procedures, can benefit from transmyocardial laser revascularization (TMR). But the underlying principle of TMR still remains unclear. This study reports on a histological analysis of eight patients, in whom a total of 250 channels had been created, who died after TMR. The TMR channels were created by a CO2 laser surrounded by a zone of necrosis with an extent of about 500 microns. In the hearts of patients who died in the early postoperative period (1 to 7 days postoperative), almost all channels were closed by fibrin clots, erythrocytes, and macrophages. There were no obvious connections between the channels and the ventricular cavity. In specimens from patients, who died 2 or more weeks after the procedure, a granular tissue with high macrophage and monocyte activity was observable. Within this tissue, we observed a developing network of capillaries. Otherwise, the tissue filling the channels did not substantially differ from scar tissue. We failed to observe connections between the ventricular cavity and the new capillaries. Whether these vessels within the closed channels have any impact on myocardial perfusion remains unclear, but it seems unlikely that the clinical effects of TMR are based on the principle of the amphibian heart.

[Histomorphology after transmyocardial laser revascularization]. / Histomorphologie nach transmyokardialer Laserrevaskularisation.

From 11/1994 to 4/1997 we enrolled 140 patients with diffuse CAD refractory to maximum antianginal therapy who are not candidates for PTCA or CABG for transmyocardial laser revascularisation (TMLR). Of these patients aged 63.5 +/- 15 years, 98 had coronary 3-vessel disease, and the average left ventricular ejection fraction was 44%. Eleven out of these 140 patients died from different reasons (pneumonia, myocardial infarction, septicemia). Seven patients who died between the 1st and 20th postoperative day underwent a postmortem examination with histological analysis of the areas treated by TMLR. On the seven investigated ventricles a total of 220 channels were created. The predominant finding in specimens within five days after TMLR was recently closed channels. Furthermore, a zone of necrosis with an average extension of 500 microns on each side of the channel was evident. Many changes were noticeable in specimens from patients who died two or three weeks after TMLR. Freshly clotted material had been replaced by a granular tissue of variable density. High macrophage and monocyte activity was evident. The extent of this cellular activity could be depicted by staining with a special proliferation marker, such as MiB. On the one hand numerous dividing macrophages were observed, on the other, active fibroblasts indicative for the transformation into scar-like tissue. After staining for type-4-collagen, typical for the basal membrane of capillaries, a large number of stained structures was noticeable in the closed channel lumen. Numerous garlandlike structures became visible under higher magnification. By CD 31 incubation, these structures, were found to be lined with endothelium. Further research will be required to indicate whether the laser channels later are partially or completely open, from where the capillaries are supplied, and whether they even connect to the ventricle lumen. But in conclusion, it seems unlikely, that TMLR follows the mechanism of the amphibian heart.

[Legionella pneumonia: pulmonary and extrapulmonary findings]. / Legionella-Pneumonie: Pulmonale und extrapulmonale Befunde.

Pulmonary and extrapulmonary findings in legionelloses generally do not permit any aetiological conclusions. The extrapulmonary phenomena are epiphenomena that can possibly be traced to the effect of a toxin.

[CEA as a tumor marker on the cell surface and in the exudate. Comparison in thoracoscopy examined pleural effusions]. / CEA als Tumormarker auf der Zelloberfläche und im Exsudat. Vergleich bei thorakoskopisch untersuchten Pleuraergüssen.

A prospective comparison was conducted in 43 patients to assess comparatively the ranking of cytology and CEA determined in the pleural effusions and by immunocytology on the cell surface (the latter two compared with each other) and then juxtaposed with the information obtained by histology via thoracoscopy. It was found that the yield achieved by cytology was comparable with that obtained by immunocytology. The maximum sensitivity was established with the adenocarcinoma.

[Immunohistochemical demonstration of extracerebral toxoplasmosis in AIDS]. / Immunhistologischer Nachweis der extrazerebralen Toxoplasmose bei AIDS.

Tissue slides obtained at autopsy from 80 cases with AIDS were studied immunhistochemically for infection with Toxoplasma gondii. In 35 cases (43.75%) toxoplasmosis could be found: in 22 cases (27.5%) only cerebral, in 9 cases (11.25%) cerebral and extracerebral and in 4 cases (5%) only extracerebral. Necrotizing lesions, due to the parasite could be seen in brain, heart, lungs, pancreas, adrenal glands and testis, only intracellular trophozoites without tissue damage in GIT, liver, lymphnodes, spleen, prostate, kidney and gl. parotis. The trophozoites and pseudocysts could be clearly demonstrated by immunohistochemistry.

Osteomyelitis due to Cryptococcus neoformans in advanced age. Case report and review of literature.

In an 84-year-old man cryptococcosis with a pronounced osteomyelitic course (involvement of a rib, two thoracic vertebrae, the sacrum and a femur) was diagnosed histologically post mortem, thus directing attention to cryptococcosis in advanced age. The presumptive chronic course of the Cryptococcus neoformans (Cr. n.) infection in this patient was ascribed to chronic kidney failure, diabetes mellitus and chronic obstructive lung disease. Special reference is made to the mycological and radiological diagnosis of cryptococcosis of the bones as well as to its pathogenesis, therapy and epidemiology.

Mucosal recipient-type mononuclear repopulation and low-grade chronic rejection occur simultaneously in indefinitely surviving recipients of small bowel allografts.

Lewis rat recipients of long-term, surviving, orthotopic Brown-Norway rat intestinal allografts, initially treated with cyclosporin A (CyA) or FK 506, were evaluated for their functional capacity and morphology over 1 year after the immunosuppressive therapy had been discontinued. Functional parameters such as nitrogen and fat balances, maltose absorption, blood chemistry, hematologic studies, and the weight gained by the allografted animals did not differ from those of syngeneically grafted or age-matched normal animals. Immunohistochemical studies showed that the lamina propria of the allografts was repopulated with recipient MHC class II+ mononuclear cells and that a normal distribution of T helper, T suppressor/killer, and IgA+ plasma cells had occurred. However, fibrous replacement of the mesenteric lymph nodes and Peyer's patches were detected in all, and an inflammatory obliterative arteriolopathy developed in the mesenteric vasculature of half of the allografted animals. No such findings were observed in recipients of syngeneic grafts. These results demonstrate that the limited use of potent immunosuppressive agents immediately after transplantation averts rejection and is followed by recipient-type mucosal lymphocytic repopulation. Simultaneously, a clinically not recognizable chronic rejection evolves. This suggests that the timely diagnosis of chronic rejection may not be possible with the use of standard tests of gut function and random mucosal biopsies alone.