Biomedical subjects
Publications and source records attributed to B Heymer.
A case of dentinogenic ghost cell tumor, that has originated peripherally in the jaw, is presented and the literature reviewed with particular reference to the origin of the tumor. The total number of central and peripheral cases reported in the English literature is 10 and although mucosal infiltration is common, peripheral origin of the neoplasm could be verified in only 3 cases.
BACKGROUND: We report on 9 infants with severe combined immunodeficiency (SCID), who additionally showed signs of Omenn syndrome with an exfoliative dermatopathy, alopecia, enlarged lymph nodes, a hepatomegalia and a striking blood eosinophilia. The immunological evaluation revealed the characteristic abnormalities of SCID with cellular and humoral immunodeficiency. All patients however had the unusual finding of mature T cells in the peripheral blood. By HLA typing these cells were noted to be of maternal origin in 5 patients. In the other 4 patients the T cells were of host origin. We asked for additional differences between both patient groups. METHOD: Both patient groups were analyzed and compared with regard to case histories, clinical, laboratory and histopathological parameters. RESULTS: No clinical or laboratory differences could be detected. The histomorphologic analysis of patients with or without maternal T cells was identical. The skin biopsies showed dense cell infiltrations of lymphocytes, histiocytes and eosinophils, in the enlarged lymph nodes the latter two cell types predominated. Therefore the only difference between the 2 patient groups was the presence or absence of maternal T cells. CONCLUSION: Since the Omenn syndrome is found in association with maternal as well as patient derived T cells, we postulate that the peculiar symptoms of this syndrome are the result of a T cell induced inflammatory reaction, similar but not identical to a graft versus host reaction, occurring on the basis of an inborn SCID.
We have studied four cases of fatal B-cell lymphoproliferative syndrome (LPS) developing among 333 patients (incidence 1.2%) treated with allogeneic bone marrow transplantation (BMT). All four patients had received a T-cell depleted graft. Onset of the first clinical symptoms (palpable lymph node enlargement in three and IgA-lambda paraproteinemia in two patients) occurred between 41 and 188 days post-BMT (median 76 days). The course of the LPS was rapidly progressive in all cases, leading to death in 2-5 weeks. The peripheral blood showed progressive pancytopenia with disproportionally high numbers of activated NK cells, apparently compensating for the T-cell deficiency. Post-mortem histological studies disclosed polymorphic B-cell proliferations, most pronounced in the lymph nodes, spleen, liver, lungs and kidneys. Lymphohemopoietic cells were of donor origin in three patients. In the fourth patient, graft failure suggested a host origin for the proliferating cells. Immunophenotyping and gene rearrangement analysis revealed polyclonal proliferation in one patient, monoclonal proliferation in another patient, and an oligoclonal pattern in the other two patients. The clinical behavior of the LPS was independent of clonality. Immunohistologically, the proliferating cells showed characteristics of relatively mature B-cells in three cases, and pre-B-cell features in one case. Epstein Barr virus (EBV) serology indicated seroconversion (primary infection) in one child, and chronic active EBV infection in both adults. EBV DNA as well as EBV nuclear antigen (EBNA) were detected in infiltrated tissues of all four patients. The labeling pattern on in situ hybridization suggested a replicative EBV infection comparable to that in lymphoblastoid cell lines. We conclude that EBV-associated LPS developing as a result of post-transplant immunodeficiency is a distinct clinicopathologic entity, differing from non-Hodgkin's lymphoma (including Burkitt's lymphoma) and infectious mononucleosis of the immunocompetent host.
A full-term 46,XY female newborn presented with respiratory failure due to a right-sided diaphragmatic hernia. During surgical repair, exploration revealed isolated dextrocardia and hypoplasia of the right lung. Neither gonads nor wolffian or müllerian structures could be palpated. Cardiac catheterization demonstrated defects of the ventricular septum, hypoplasia of the right pulmonary artery, persistence of the left vena cava superior and a patent ductus arteriosus. Anthropometric data were normal at birth, but fell below the 3rd percentile during follow-up. Body proportions displayed a predominance of the upper compared to the lower segment. Endocrine studies indicated no defect of steroid biosynthesis and no functional gonadal tissue. Using genetic analyses of various loci within the testis-determining region of the Y chromosome, a mutation could not be detected. The patient died from pneumonia at the age of 19 months. Postmortem examination confirmed the diagnosis of gonadal agenesis.
1. The Omen-syndrome is not a disease on its own, but a complication of congenital SCID. 2. In contrast to patients with classical SCID, patients with Omenn-syndrome possess mature T-cells, which are either of maternal or of host origin. 3. These T-cells are involved in the pathogenesis of the characteristic tissue changes, in particular of skin and lymph nodes (Langerhans-histiocytosis with eosinophilia). 4. The detection of immunodeficiency in Omenn-syndrome is difficult since the lymph nodes are enlarged in contrast to patients with classical SCID. The histomorphological analysis of lymph nodes in Omenn-syndrome is considerably complicated by secondary changes closely resembling dermatopathic lymphadenopathia.
Most inborn immunodeficiency syndromes clinically become overt by complicating infections, e.g. by BCG-infection after BCG-vaccination. The diagnostic approach often is hampered by an atypical histomorphological picture of the infection caused by the underlying immune defect. We examined biopsies of different organs in 18 infants with severe combined immunodeficiency syndrome and BCG-infection. A number of unusual histomorphological patterns of BCG-infection were found not yet published previously. There was a correlation between histomorphological features and immunological data or clinical course in most cases.
Reticular Dysgenesis (RD) basically represents a lymphopenic severe combined immunodeficiency (SCID) in association with congenital agranulocytosis. It is presumed that RD results from a primary defect of pluripotent hematopoietic stem cells (HSC). Alternatively RD might be due to an alloreaction induced by T-cells derived from intrauterine transfusion of maternal cells into an immunoincompetent host. In the past 15 years, among 49 newborns with SCID taken care of in the University Hospital of Ulm, 5 children (4 boys, 1 girl) exhibited the characteristics of RD. In 3 of 4 cases studied, maternal T-cells were detected by HLA-typing. All 3 children showed signs of graft-versus-host-disease (GvHD), confirmed histologically. However, 9 of 45 newborns with SCID without congenital agranulocytosis also disclosed maternal T-cell-engraftment; 5 of the 9 had signs of GvHD. Therefore, it is unlikely that RD is caused by GvHD secondary to maternofetal transfusion. The fact that erythropoiesis, thrombopoiesis and the monocyte-macrophage-system basically are intact argues against a global maturation defect of HSC in RD.
In the present survey the pathohistologic substrate of the major thyroid diseases (functional disturbances, goiters, inflammations, tumors) occurring in childhood is described. In this context the functional morphology (correlation of structure and function) and the immunohistology of the thyroid is reported in detail. Finally, it is discussed under which conditions histologic studies of the thyroid are meaningful for the diagnosis.
An ischemic colitis of the descending Colon and Sigma in 3 patients following aorto-iliacal reconstruction was caused by embolism of cholesterol crystals. In all cases the stump pressure of the inferior mesenteric artery measured more than 40 Torr as an empiric value. Therefore a good collateral blood flow could be expected. Nevertheless a malperfusion of the left Colon occurred. These cases of postoperative ischemic colitis were caused by multiple cholesterol crystal emboli in the arterioles of the colon descendens and Sigma. The mobilisation and embolism of arteriosclerotic material during aorto-iliac reconstruction must be responsible for the unfortunate event. Awareness of a bowel ischemia following abdominal aortic surgery and immediate endoscopic control should lead to an early diagnosis and a higher survival rate. A decision to redo operation with left hemicolectomy is required at an early stage.
The impact of aggressive chemotherapy on reproductive and endocrine gonadal function was prospectively studied in 44 patients with germ cell tumors. Diagnostic procedures to determine gonadal toxicity consisted of hormone determinations, semen analyses, interviews with a standardized questionnaire, and gonadal histology. After chemotherapy all patients showed elevated serum levels of follicle-stimulating hormone (FSH) and azoospermia due to germ cell and stem cell loss. Recovery of spermatogenesis, as indicated by normalization of serum FSH levels and sperm density, occurred in 77% of the patients 25-60 months after cessation of chemotherapy. In all patients serum testosterone and luteinizing hormone (LH) values remained within normal limits after therapy indicating resistance of Leydig cells to cytotoxic drugs. Three patients fathered four healthy children after completion of chemotherapy. These data suggest significant reproductive dysfunction in all men treated for germ cell tumors. However, most patients showed late and complete recovery of spermatogenesis. In contrast, endocrine gonadal function was unaffected after chemotherapy in all patients. FSH and LH are feasible markers to assess drug-induced gonadal toxicity.
Based on a retrospective evaluation of 107 patients with congenital venous angiodysplasia of the Type Klippel-Trenaunay (n = 76) and Type Servelle-Martorell (n = 31) the frequency and pathogenesis of aneurysm formation in the venous system has been analysed. The vascular patterns include both cylindric ectasias and fusiform aneurysms with an incidence of approximately 40%. Preferred locations are subcutaneous drainage veins, the popliteal, external iliac vein and atypic communicating veins between the superficial and the deep venous system. Complications of the aneurysm such as local thrombosis, recurrent pulmonary embolism or bleeding from rupture were not observed. From a pathogenetic point of view the aneurysm formation in venous angiodysplasias results probably from two causative factors, i.e., a congenital weakness of the venous wall (inborn error?) and an abnormal hemodynamical stress situation. The latter is caused by concomitant malformations of the deep venous system (avalvulia, hypo- and/or aplasia). The persistent intermittent venous hypertension associated with a more or less pronounced increase of the venous volume in the affected venous system of the limb results in a deep venous insufficiency respectively venous reflux disease. Surgery is indicated under two conditions: a) in the presence of aneurysm complications or b) for the elimination of a pathological short circuit flow in some drainage veins. Antireflux surgery, e.g., venous valve transfer form the brachial vein, is up to recently still in a stage of experimental-clinical investigation. The therapy of choice is predominantly conservative, i.e., external compression bandages or stockings to reduce the deleterious effects of a chronic deep venous insufficiency respectively venous reflux disease.
Interstitial pneumonia (IP) is currently the most frequent and severe complication of allogeneic bone marrow transplantation (BMT). Post-BMT-IP is due partially to infection by cytomegalovirus (CMV-IP) and partially to idiopathic induction (IIP). Because of the different therapeutic consequences it is important to distinguish between these two kinds of pneumonia. Therefore, the validity of immunohistochemistry (IHC) and in situ hybridization (ISH) for the differential diagnosis of CMV-IP and IIP was studied. The investigations were performed using postmortem tissue samples (lung) of 23 patients decreased after allogeneic BMT. In 22 of the 23 patients the primary cause of death was IP (CMV 13x, idiopathic 7x, pneumocystis 1x, toxoplasmosis 1x). One patient died from thrombopenic cerebral bleeding. All 3 CMV-detecting systems tested disclosed certain advantages and disadvantages. The sensitivity of routine histology was 12/13 (92.3%), of IHC 13/13 (100%), and of ISH 12/13 (92.3%). The specificity corresponded to the order: ISH greater than IHC greater than histology. The application of ISH and IHC did not change significantly the routine histologic classification of pneumonias into CMV-IP and IIP. The validity of the three procedures used for detecting CMV in patients after allogeneic BMT is discussed in detail.
Three cases of congenital brain tumours are reported, which presented with signs of increased intracranial pressure soon after birth, giving rise to the suspicion of a cerebral haemorrhage or of hydrocephalus. Correct diagnosis of tumour was established by computerised tomography, which additionally demonstrated a concomitant haematoma in each case. Two of the newborns had a primarily fatal course, with no specific treatment of the tumours being feasible. The remaining child underwent two operations, experiencing an unhindered neurologic and mental development thereafter. The histologic diagnoses were spongioblastoma and medulloblastoma in the first two cases, and ganglioneuroblastoma in the last. A conspicuous clinicopathologic feature of this neuroblastoma was the marked change in its growth pattern, revealing a higher degree of histologic differentiation and less malignant biological behaviour when tumour regrowth occurred. The diagnostic, therapeutic, and prognostic implications for this special clinicopathologic condition are discussed, with a review of the relevant literature.
This paper is a survey of the histomorphology of experimental listeriosis based on cooperative studies performed within the past ten years. The influence of various parameters of the infectious agent (pathogenic Listeria monocytogenes serovar 4b, nonpathogenic Listeria innocua serovar 6b etc.) as well as of the host (euthymic NMRI-mice conditioned with dextran sulfate 500 or cyclosporin A, athymic nude mice etc.) on the course, morphology and outcome of the Listeria infection was investigated. From the experimental models used and the studies performed much could be learned concerning the factors that determine the histomorphological manifestations of listeriosis in humans.
The experimental infection of murine hosts with Listeria monocytogenes is often used as a model for cell-mediated immunity. However, the natural immunity or non-specific resistance to listeriosis can be influenced by the parasite itself and also by a wide array of endogenous and exogenous host factors. The most important host factor in inbred mouse strains is their genetically determined susceptibility or resistance to Listeria monocytogenes. Secondly, the age of the mice is crucial for the outcome of infection. Resistance is only slowly developed by newborn mice, while aged mice possess an increased non-specific resistance as compared to young adult animals. Resistance is further influenced by the nutritional status, by pregnancy or by a simultaneous second antigenic stimulation. Regarding exogenous factors, macrophage blocking agents can totally abolish the resistance to listeriosis, while a lot of immunomodulating agents, such as BCG, killed Bordetella pertussis or Propionibacterium acnes organisms, lipopolysaccharides, suramin etc., can either increase or decrease the resistance. The mononuclear phagocyte system seems to be the main target of all these immunomodifiers. The timing between listeria infection and application of the immunomodulator determines the effect on non-specific resistance. A simultaneous injection of parasite and immunomodulator results in a decrease of resistance, while the application of immunoadjuvants several days before infection can dramatically increase the resistance to listeriosis. The delicate equilibrium of the mononuclear phagocyte system must therefore be taken into account, when infection with Listeria monocytogenes is used to test for immune-modifying agents, which are intended for use in humans or animals.
Biopsy and autopsy specimens from 22 patients with cytomegalovirus (CMV) infections were investigated by means of in situ hybridization (ISH) to detect viral DNA and by immunohistochemistry (IHC) to visualize viral proteins. Both methods proved to be valuable tools for histopathology. ISH sometimes recognized cells that did not show typical CMV inclusions. An antiserum against the full spectrum of viral proteins (non-infectious enveloped particles) detected most cytomegalic cells in disseminated and organ-limited infections. An antiserum against a recombinant polypeptide (XP1) was particularly useful in connatal CMV infections and organ-limited infections. We have demonstrated that IHC and ISH studies in parallel are the best approach to the detection of CMV infections in pathological specimens.
A girl aged 12 years and 10 months presented with deepening of the voice first noted 7 months earlier. Pubertal development was almost completed. The girl had regular monthly menses and no signs of hirsutism, clitoris enlargement or Cushing's disease. Serum testosterone was about threefold above normal, whereas dehydroepiandrosterone was in the upper normal range. The 17-ketosteroids as well as the gas-chromatographically analyzed 5 alpha and 5 beta derivatives of testosterone from urine were slightly increased. Other serum and urinary steroids were normal. Dynamic tests of the endocrine function exhibited inconclusive results. Ultrasonography revealed no ovarian cysts. A small, left-sided adrenal mass was identified by computed axial tomographic scan and removed by surgery. There were no signs of local metastasis nor of vascular extension. The histopathological diagnosis was adrenocortical carcinoma. 5 months after surgery, the preoperatively elevated steroid levels had returned to normal.
Between June 1980 and June 1986, 345 inguinal explorations for intrascrotal space-occupying lesions were performed. In 47 patients benign testicular tumors were diagnosed (13.5%). In 32 of the 47 tumors (68%), the testis could be preserved by excision or enucleation of the tumor. In the remaining 15 patients a high semicastration was carried out: in 12 cases macroscopic examination or frozen section revealed doubtful benignity (6 Leydig cells tumors, 5 dermoid cysts and 1 epidermoid cyst), in 3 patients because of extensive involvement of the testis. In a follow-up period of 1-7 years none of the patients has shown evidence of tumor recurrence or metastasis. Changing the concept of not incising the parietal tunica of the testis and regarding clear-cut macroscopic and histological criteria of benignity on frozen section will safely lower the testicular loss rate from up to 80% to about 30% when benign tumors are encountered.