Gastrointestinal side-effects of octreotide during long-term treatment of acromegaly.

Gastrointestinal side-effects of prolonged therapy (greater than 2 yr) with the long-acting somatostatin analog octreotide were studied in 10 acromegalic patients. After 2 yr of therapy, 6 of 10 patients had newly developed gallstones, complicated by cholangitis and jaundice in 1. Serum vitamin B-12 concentrations declined in all 10 patients [from 380 +/- 32 to 172 +/- 21 pmol/L (mean +/- SE); P = 0.023] and became abnormally low in 4. Gastric biopsy specimens, obtained during gastroscopy (9 patients), showed moderate to severe active gastritis, with damage to the superficial and deeper layers of the mucosa in 9 of 9 and focal atrophy in 7 of 9 patients. Campylobacter pylori was found in the antral mucosa in 8 of 9 patients. Although information is lacking on similar studies in untreated acromegalic patients, we suggest that patients receiving chronic octreotide therapy be closely monitored for these and possible other side-effects related to gastrointestinal actions of octreotide.

Epstein-Barr virus and carcinomas. Expression of the viral genome in an undifferentiated gastric carcinoma.

The Epstein-Barr virus (EBV) is associated with undifferentiated nasopharyngeal carcinomas (NPCs). Recently, EBV DNA has been demonstrated also in some cases of gastric carcinoma with similar morphology as undifferentiated NPC. Here we report on the expression of EBV genes in a gastric undifferentiated carcinoma of nasopharyngeal type (UCNT). The small EBV-encoded nuclear RNAs, EBERs, were expressed in all tumor cells. The BZLF1 transactivator protein, which disrupts viral latency, was detectable in a small subset of tumor cells. The latent membrane protein and the nuclear antigen EBNA2 were not expressed. These results indicate that lytic EBV infection may be possible in undifferentiated epithelial cells. Our findings add to the growing body of evidence suggesting a strong association of gastric UCNT with EBV and point to the possibility of an involvement of the virus in the pathogenesis of this neoplasm.

So-called peritoneal implants of ovarian carcinomas. Problems in differential diagnosis.

The aim of this paper is the differential-diagnostic distinction of peritoneal 'implants' of serous ovarian tumours from morphologically similar lesions in the peritoneum. The authors investigated 22 cases of ovarian carcinomas, 'implants' of ovarian carcinomas, reactive mesothelial proliferates, endosalpingiosis, benign and malignant mesotheliomas, as well as papillary carcinomas of the pelvic peritoneum with conventional histological stainings and immunohistochemical methods (immunoperoxidase, ABC method). The cells of almost all mentioned lesions express cytokeratin, only the cells of the reactive mesothelial proliferates are partially keratin-negative. CEA was not detected in any of the lesions. Alpha-1-antitrypsin was present in the cells of some ovarian carcinomas and their implants. Lysozyme was found focally in some ovarian carcinomas and in some reactive mesothelial proliferates. An exact differentiation of peritoneal 'implants' as metastases of ovarian carcinomas or autochthonous neoplasias in the course of multifocal tumour development is not possible on the basis of our immunohistochemical findings.

Pulmonary blastomas. Immunohistochemical investigations of three cases.

Three cases of pulmonary blastoma (PB) were investigated microscopically with conventional stainings and immunohistochemically with monoclonal antibodies to cytokeratin, vimentin, desmin and neurofilament protein. The tumors differed in terms of morphology as well as of immunohistochemistry. Two were epithelial and mesenchymal mixed tumors, and the remaining one was a monophasic tumor of a typical blastemic character. The two mixed tumors also differed from each other. In one of them, the epithelial and mesenchymal component expressed cytokeratin and vimentin in a clear-cut manner without any transition. The other mixed tumor displayed a gradual epithelial-to-mesenchymal transition accompanied by a switch in the expression of cytokeratin and vimentin. The third tumor was of pure mesenchymal origin, expressing vimentin in the majority of cells and desmin in few cells. It is concluded that the PB is a morphologically and histogenetically heterogeneous tumor. Metaplastic changes may take place within a PB and make the recognition of embryogenesis more difficult.

Macrophages (phagocytic-histiocytic reticular cells) in reactive-inflammatory lesions of the bone marrow and in myelodysplastic syndromes (MDS). An immunohistochemical and morphometric study by use of a new monoclonal antibody (PG-M1).

An immunohistochemical and morphometric study was performed on trephine biopsies of the bone marrow in 52 patients (28 males/24 females; age 68 years) with various subtypes of myelodysplastic syndromes (MDS) to determine the number of macrophages (phagocytic-histiocytic reticular cells). Quantifications included the haemosiderin-storing subpopulation (Prussian-blue reaction) of this lineage as well as the iron-free compartment. The latter was identified by a new monoclonal antibody (PG-M1) which is specifically directed against histiocytic reticular cells. Bone marrow specimens of individuals without haematological disorders and those showing reactive lesions served as controls. In comparison with the normal bone marrow and inflammatory changes (i.e. rheumatoid arthritis) 23 of the 52 patients with MDS revealed a significant increase in macrophages. This increase encompassed not only the iron-laden subpopulation but also the total number of phagocytic reticular cells. Accumulation of macrophages in MDS was speculated to be due to a premature and enforced degradation of dysplastic cell elements leading to phagocytosis of haemosiderin and debris material. Moreover, cells of the monocyte-macrophage system could be involved in the complex pathomechanism of fibrillogenesis, since in a considerable percentage of patients with MDS, an increase in reticulin (argyrophilic) fibres was noticeable. Our finding of an expansion of the macrophage compartment in about half of the patients with MDS is in keeping with results of cell culture studies on colony formation of granulocyte-macrophage precursors (CFU-GM).

Megakaryocytopoiesis in bone marrow biopsies of patients with acquired immunodeficiency syndrome (AIDS). An immunohistochemical and morphometric evaluation with special emphasis on myelodysplastic features and precursor cells.

In 25 patients (22 males, 3 females--median age 39 years) with AIDS (CDC stages IV A-D) and no preceding myelotoxic therapy, morphometry and immunohistochemistry (CD 61-Y 2/51) was performed on trephine biopsies of the bone marrow to evaluate the megakaryocytic lineage. In comparison with megakaryocytes in the myelodysplastic syndromes (MDS) significant differences were evident. In AIDS this cell population revealed a size distribution within the normal range (control group) and no predominance of micromegakaryocytes characteristic for MDS. Furthermore, by determination of the form factors more irregular shapes of cell and nuclear perimeters could be shown. Finally, a not-evaluated number of precursors (promegakaryoblasts) was calculable. Particularly in those patients (n = 15) with AIDS-related severe thrombocytopenia the missing increase in the relative amount of promegakaryoblasts was conspicuous. This result was strikingly different from findings in idiopathic (autoimmune) thrombocytopenia and suggested an impairment of progenitor cell proliferation and differentiation in the acquired immunodeficiency syndrome. In conclusion, morphometry in combination with immunohistochemistry failed to establish characteristic myelodysplastic aspects of the megakaryocytic lineage in AIDS. For this reason, bone marrow lesions in this disorder should be properly termed HIV-myelopathy and not myelodysplasia.

Pro-megakaryoblasts in bone marrow tissue from patients with primary (idiopathic) osteo-myelofibrosis (agnogenic myeloid metaplasia). An immunomorphometric study on trephine biopsies.

An immunomorphometric study was performed on bone marrow biopsies from 40 patients with primary osteomyelofibrosis--OMF, (agnogenic myeloid metaplasia) by employment of a monoclonal antibody against glycoprotein IIIa (Y2/51) to determine the number of pro-megakaryoblasts. Specimens from 15 individuals without any hematological disorder served as controls. With reference to the pertinent literature on megakaryocyte precursors and following a pilot study on corresponding smears, in tissue sections pro-megakaryoblasts were characterized by a size of 42.1 +/- 2.6 microns 2 (diameter 7.5 +/- 0.3 microns). In comparison with controls, in OMF no relevant increase in the number of pro-megakaryoblasts per square and cubic millimeter bone marrow was evaluable. The relative frequency of these precursors was significantly reduced due to an increase in the total amount of conspicuously large and abnormal megakaryocytes. Statistical analysis failed to reveal any correlations between counts for pro-megakaryoblasts or the total number of Y2/51--positive megakaryocytic elements with the density of argyrophilic fibers (determined by morphometry) or the platelet values. Our findings imply that in OMF the marked increase in circulating progenitor cells of the megakaryocyte lineage may be generated by extramedullary, probably splenic hematopoiesis. Moreover, the evolution of medullary fibrosis is thought to be associated with the striking predominance of large atypical, possibly overaged and hyperpolyploid megakaryocytes and not with an increase in precursor cells.

Cerebral lymphoma in AIDS. Clinical, radiological, neuropathological and immunopathological study.

Neuropathological findings from 8 individual cases of cerebral lymphomas in AIDS patients with consideration of the clinical, radiological, immunopathological, and other pertinent data selected from a series of 80 patients between 1985 and 1989 were studied. A wide variation in pathology was noted among our cases. It has been shown that lymphoma as a neuropathological diagnosis can coexist with a wide range of other characteristics, including toxoplasmosis, glial nodules, neuronophagia, degeneration, bleeding, hypoxia, progressive multifocal leucoencephalopathy, and myelopathy, although none of these attributes appeared more than casually interrelated. In general, the late-stage manifestations of lymphoma as were observed in this study, tended to be poorly localized, often simultaneously meningeal, perivascular, and diffuse in character. An important distinction between cerebral lymphomas of AIDS and non-AIDS patients is the highly atypical, clinically unreliable computer tomographic signals observed in several of our cases. Five of the six immunopathological investigations showed a preponderance of B-cell markers, corresponding in toto to high-grade non-Hodgkin lymphoma. One case exhibited immunohistological markers typical of Hodgkin's lymphoma (antibody CD-30). Of 6 obtainable serum specimens from our 8 cases, 4 showed high (greater than 2000) IgG titers against the EBNA-1 antigen of Epstein-Barr virus (EBV), of these three had IgM titers further supporting viral reactivation. One showed a normal IgG titer, yet with a significantly raised IgM titer.

Oral manifestations of AIDS-associated non-Hodgkin's lymphomas.

While B-cell lymphomas are frequently found in AIDS patients, reports on oral manifestations are rare. Among a group of 465 HIV-infected patients 5 presented with primary oral manifestations of a malignant B-cell lymphoma. The primary site of manifestation was the maxilla in 3 cases and the mandible in 2 cases. Based on the histological and immunohistochemical examination the tumors were differentiated as Burkitt's lymphoma (n = 1), as anaplastic large cell (ALC) lymphoma of the B-cell type (n = 1), as high-grade non-Hodgkin's lymphoma not classifiable according to the Kiel classification (n = 1), as immunoblastic-plasmoblastic lymphoma (n = 1), and as centroblastic lymphoma (n = 1). Serum samples were negative for HTLV-I antibodies in 5/5 cases.

Vessel preservation with glycerol: an experimental study in rats.

Arterial and venous allografts (aorta and femoral vein or artery) of Sprague-Dawley rats were preserved with glycerol (98%) or by lyophilization and subsequently implanted in Wistar rats. The grafts were removed for histologic examination of vessel patency on days 1, 30, 60, and 100 postoperatively. Whereas the glycerol-preserved vessels exhibited a high patency, the results obtained with the lyophilized vessels were less favorable. Lyophilized veins could not be successfully implanted.

Peripheral T-cell lymphomas.

The development of T cells from stem (progenitor) cells to effector cells results from a two-wave process of proliferation and differentiation. The cells of the first differentiation wave are the precursor T cells, and those of the second differentiation wave are peripheral T cells. In the first differentiation wave, resting/circulating naive antigen-reactive T lymphocytes are produced which differ from each other in their antigen receptor-specificity. In the second differentiation wave, those T lymphocytes multiply whose antigen receptors have found the corresponding antigen. Thus three major forms of differentiation can be distinguished in the peripheral T cells: (1) resting/circulating naive antigen-reactive T cells, (2) activated T cells, and (3) effector T cells and memory T cells. In addition, there are at least three major organ-restricted sublines of peripheral T cells, i.e., nodal T cells, mucosa-associated T cells, and skin-associated T cells. Thanks to the availability of markers for most of the above-mentioned T-cell sublines and differentiation forms, all these cellular forms can be associated with certain lymphoma types, i.e., lymphomas of T-cell type can be divided into categories of precursor T-cell lymphomas and peripheral T-cell lymphomas. The peripheral T-cell lymphomas can be subdivided into those derived from lymph nodal, mucosal, and cutaneous T cells. The gut mucosal T-cell lymphomas are associated with enteropathy. The lymph node, mucosal, and cutaneous T-cell lymphomas can be further subdivided into those in which all tumor cells are similar to recirculating resting (nonactivated) T cells, those in which some of the tumor cells resemble activated T cells, and those in which all tumor cells resemble activated T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Sinus histiocytosis with massive lymphadenopathy. Skeletal involvement.

A 64-year-old female patient has been suffering from sinus histiocytosis with massive lymphadenopathy (SHML) for 2 years. After 12 months of illness, the patient developed swelling and pain in various skeletal regions. Scintigraphic, radiological and CT imaging revealed multiple osseous lesions. Subsequent biopsies yielded the histomorphological findings typical for SHML. After operative resection of the left cuboid, which was the most painful region during walking, the defect was filled with an autologous bone transplant. At this time no other osteolytic region was treated surgically, because the patient had first to undergo ENT treatment.

[Leiomyosarcoma of the inferior vena cava. Diagnosis--therapy--prognosis]. / Das Leiomyosarkom der Vena cava inferior. Diagnostik--Therapie--Prognose.

Leiomyosarcoma of the vena cava inferior is a mesenchymal tumor originating from the smooth muscle fibers of the vascular wall. This tumor is usually slow-growing and expansile growth. Prior to the sonographic and computer-tomographic era the tumor was usually only discovered during autopsy or surgery without any preoperative suspicion. Today, the most efficient imaging methods for exact localization, delineation or demonstration of relations to the vascular lumen and local extent are sonography and computer tomography. Caudal cavography is called upon for preoperative demonstration of the venous collateral circulation and thrombotic vascular occlusion.

Intraoral defect coverage with muscle flaps.

PURPOSE: This study investigated whether wound healing after the use of purely muscular flaps for intraoral defect coverage is negatively influenced by insipient muscular atrophy and the absence of a covering layer. MATERIALS AND METHODS: In an experimental study, microsurgical transplantation of muscle flaps from the anterior abdominal wall was carried out in 18 Lewis rats. A nerve anastomosis for motor reinnervation was not performed. Atrophy of the muscle flaps was determined by measuring the reduction of their size and weight after 3, 8, and 20 weeks. In the clinical part of the study, free muscle transplants from different donor regions (vastus lateralis, pectoralis major, internal oblique, and temporalis muscles) were used for defect coverage in various areas of the oral cavity. To study epithelization, punch biopsy specimens from the muscle surface were taken at periods of 2 to 4 weeks up to 6 months for histologic evaluation. Final evaluation of reconstruction results with special regard to speech, tongue mobility, mouth opening, chewing, and swallowing took place after 6 months. RESULTS: In the experimental study, average weight loss of the muscle flaps was 67% after 20 weeks, and the remaining surface area was 71%. The number of myocytes was only about 30% compared with control muscles, and parts of the flap appeared as a thin fibrous membrane. Clinically, this atrophy led to restricted mobility in such areas as the floor of the mouth, the buccal plane, and the tongue. Muscle flaps covering solid structures such as bones or reconstruction plates adapted well to the transplant bed, and the atrophy of the muscle led to no constriction of the surrounding tissue. Atrophy also did not have a negative effect when muscle flaps were placed in the region of the pharyngeal wall. Epithelization started from the edges after 2 weeks and was concluded after 8 weeks in all transplants if no additional radiation was performed. The muscle tissue was sufficiently resistant so that infection, fistulization, and necrosis did not occur. CONCLUSIONS: Muscle flaps undergo considerable atrophy with a cicatricial transformation and reduction of flexibility. Despite these disadvantages they can be used in the hard palate, the alveolar crest, and in the pharyngeal wall without causing functional restriction. Because of constriction of the surrounding tissues, mobile areas such as the buccal plane, the floor of the mouth, and the tongue are not suitable as sites for muscle transplants.

Borrelia burgdorferi-associated cutaneous B cell lymphoma: clinical and immunohistologic characterization of four cases.

Four patients with low-grade malignant B cell lymphoma of the skin in association with chronic Borrelia burgdorferi infection are presented. Plaque-shaped or nodular erythematous lesions with ill-defined borders were seen. Clinical progression was slow; the skin tumors occurred for up to 7 to 15 years. Extracutaneous involvement was found in only one case. Immunohistologic investigations showed an expression of B cell markers with restriction to only one light chain type and absence of T cell antigens. The growth fraction was 5% to 30%, as shown with the monoclonal antibody Ki-67. The immunoarchitecture of the tumors in three patients was unusual compared with established criteria for cutaneous B cell lymphoma and revealed similarities to mucosa-associated B cell lymphoma. Some immunohistologic heterogeneity may indicate the development of monoclonal proliferation that originated from different phases of B lymphocytic differentiation. In three cases no clinical signs of B. burgdorferi infection were found; in one patient acrodermatitis chronica atrophicans was present. The occurrence of acrodermatitis chronica atrophicans and malignant lymphomas was frequently reported in the European literature before B. burgdorferi was recognized. These findings suggest a relation between B. burgdorferi infection and cutaneous B cell lymphoma. In geographic regions where infected ticks are present, borreliosis should be considered in patients with cutaneous B cell lymphoma.

HIV-related malignant lymphomas. A clinical and pathological study of 13 cases.

The clinical and laboratory records of 13 patients with HIV-related lymphomas diagnosed between 1983 and 1987 are reviewed. 8 cases were classified as high-grade Non-Hodgkin-lymphomas (NHL), 4 as low-grade NHL (including 2 plasmocytomas), and one as Hodgkin's disease (HD). 11 of the 12 NHL were of the B-cell lineage. The mean patient's age was 39 years. At initial staging evaluation extranodal disease was present in 10 patients, in one of them as primary central nervous system (CNS) lymphoma; 9 patients presented with stage III or stage IV involvement. 9 patients were eligible for multidrug chemotherapy. In 5 cases an initial complete remission (CR) was observed, followed, however, by CNS relapse within a few months in 3 patients. 3 patients did not respond to chemotherapy and died within 4 to 6 weeks. Of the 9 patients treated chemotherapeutically, 5 died within 1 to 5 months, 1 is still alive in CR and 3 are still alive in partial remission (PR).

Megakaryocyte precursors (promegakaryoblasts and megakaryoblasts) in the normal human bone marrow. An immunohistochemical and morphometric study on routinely processed trephine biopsies.

On routinely processed trephine biopsies of the normal human bone marrow derived from 15 patients, immunostaining with a monoclonal antibody against platelet glycoprotein IIIa (Y2/51) and morphometric measurements were performed for the determination of megakaryocyte precursor cells. Based on cell sizes and on comparison with (1) specimens stained by the periodic acid-Schiff reaction and (2) smears, the smallest elements clearly identifiable as belonging to the megakaryocyte series were classified as promegakaryoblasts. Promegakaryoblasts had a frequency of 1.7/sq mm and 140/cu mm of bone marrow and constituted about 8% of the total positively stained megakaryocytic elements; they were characterized by a size of 41.5 sq microns, a diameter of 7.7 microns, a high nuclear-cytoplasmic ratio (0.32) and a nearly circular outline of their nuclear and cellular perimeters.

Identification of a T cell lymphoma category derived from intestinal-mucosa-associated T cells.

2 cases of precursor T cell lymphoma and 37 cases of peripheral T cell lymphoma were investigated for their reactivity with the monoclonal antibody (mAb) HML-1, which recognises human intestinal T lymphocytes but not lymph-node T cells. In all but one of the lymphomas studied, the tumour cells were unreactive with the mAb HML-1. The HML-1+ lymphoma was the only tumour that was primarily localised in the epithelium and lamina propria of the small intestine, and was associated with ulcerative jejunitis and coeliac disease. This result suggests that the HML-1+ lymphoma was derived from intestinal mucosa T lymphocytes and differs from precursor T cell lymphoblastic lymphomas and nodal and cutaneous peripheral T cell lymphomas.

Macrophages in normal human bone marrow and in chronic myeloproliferative disorders: an immunohistochemical and morphometric study by a new monoclonal antibody (PG-M1) on trephine biopsies.

An immunohistochemical and morphometric study was performed on routinely processed trephine biopsies of the bone marrow in 30 normal individuals and in 90 patients with various subtypes of chronic myeloproliferative disorder. Using a new monoclonal antibody (PG-M1) directed against a formalin-resistant epitope on macrophages and by employment of the Prussian blue reaction, quantitation of this cell population was feasible. Morphometric analysis revealed that the number of iron-laden macrophages represented only a fraction of the total number of histiocytic reticular cells. As could be expected, in polycythaemia rubra vera, no haemosiderin deposits were detectable, but the content of macrophages slightly exceeded that of the normal bone marrow. In chronic myeloid leukaemia 9 of 30 patients showed a significant increase in PG-M1-positive reticular cell elements. These were consistent with pseudo-Gaucher cells, sea-blue histiocytes and intermediate cell types. Primary (idiopathic) myelofibrosis-osteomyelosclerosis was characterized by a significant increase in macrophages (25 of 30 patients). Involvement of macrophages in the complex mechanisms generating bone marrow fibrosis and angiogenesis and in bone remodelling (osteosclerosis) may be responsible for this finding.