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Biomedical subjects

P Ruck

Publications and source records attributed to P Ruck.

At least 55 records · Page 3Linked to original sources
PubMed1997

Mastocytosis: reactive or neoplastic?

Mast cells are now known to derive from CD34+ haemopoietic stem cells in the bone marrow. However, it has not yet been established whether the various types of mastocytosis, which involve tumour-like proliferation of mast cells, are true neoplastic disorders or reactive/hyperplastic conditions. In this study, tissue specimens (five bone marrow, two spleen, one skin) from female patients with histologically confirmed mastocytosis were investigated with a recently developed polymerase chain reaction assay for the determination of clonality of female cells using the human androgen receptor gene (HU-MARA). Mast cells purified to near homogeneity from hysterectomy specimens served as a control. The findings in bone marrow and skin either were not reproducible, or indicated polyclonality. However, both spleen specimens exhibited monoclonality. In addition, DNA analysis by flow cytometry was performed and revealed a diploid chromosome content with proliferation indices of under 8% in all the specimens. This is the first molecular biological study to indicate that mastocytosis is indeed neoplastic in nature.

Case-Control Studies↗
PubMed1997

Renal involvement in myeloproliferative and lymphoproliferative disorders. A study of autopsy cases.

A considerable proportion of cases of myeloproliferative and lymphoproliferative disorders exhibit renal involvement. However, it is unclear whether the cytologic features, immunophenotype or grade of malignancy of the cells infiltrating the kidney differ from those of the primary tumor. This study was performed on 120 autopsy cases with the following diagnoses: acute myelogenous leukemia (AML, n = 22; subtypes M1 + M2, n = 12, subtype M4, n = 10), chronic myelogenous leukemia (CML, n = 7), agnogenic myeloid metaplasia/myelofibrosis (AMM/MF, n = 6), acute lymphocytic leukemia (ALL, n = 6), chronic lymphocytic leukemia (CLL, n = 9), other low-grade non-Hodgkin's lymphomas (low-grade NHL, n = 24), high-grade NHL (n = 21) and multiple myeloma (MM, n = 25). Renal involvement was investigated by light microscopy and immunohistochemistry. It was found in 34% of the cases, and was most common in ALL (83%) and low-grade NHL (50%) and least common in high-grade NHL (10%) and MM (12%). Dense infiltration of almost the entire kidney was most commonly seen in AML, low-grade NHL and ALL. Infiltration was bilateral and involved both the cortex and medulla in the majority of cases. When involvement of other organs was compared with that of the kidney, the lung was found to be involved in approximately the same number of cases, but liver involvement was more common and heart involvement less common. Reactive lymphocytic infiltration of the kidney was found in 18 of the 120 cases (15%), and was distinguished from scanty tumorous infiltration by immunohistochemical staining. No major phenotypical differences were found between the tumor cells infiltrating the kidney and those of the primary tumors in the bone marrow or lymph nodes. However, in one case of CML, the cells infiltrating the kidney were negative for KP1 and chloroacetate esterase, but could be identified by reactivity for CD34. The grade of malignancy in NHL was similar in both the nodal and renal manifestations.

Adult↗
PubMed1997

Systemic mast cell disease (mastocytosis). General aspects and histopathological diagnosis.

Systemic mast cell disease/mastocytosis (SMCD) is best defined as a multitopic proliferation of cytologically and/or functionally abnormal tissue mast cells (TMC). SMCD preferentially involves the bone marrow, skin, spleen, liver, and lymph nodes. The histopathological diagnosis of SMCD may be very difficult to make, and the disease is often not considered in the differential diagnosis of lymphoreticular neoplasia. In suspected cases of SMCD, basic dyes such as Giemsa and toluidine blue are useful to demonstrate the specific metachromatic granules of TMC. The naphthol AS-D chloroacetate esterase reaction has also proved to be very reliable for enzyme-histochemical identification of TMC. Major diagnostic problems may arise in cases of malignant or "aggressive" SMCD exhibiting tissue infiltrates consisting predominantly of highly atypical, non-metachromatic TMC, which are usually also only weakly reactive for chloroacetate esterase. Immunostaining with antibodies against the mast cell-specific proteases tryptase and chymase has proved to be of great value of establishing the correct diagnosis in such cases. Anti-tryptase antibodies have major diagnostic significance due to their extremely high sensitivity and specificity. The classification of SMCD is controversial, but there is increasing support for the differentiation of at least two major subtypes that differ in prognosis: (i) a benign or "indolent" variant in which skin involvement (urticaria pigmentosa-like skin lesions) is usual, but associated malignant hematological disorders are rare; and (ii) a malignant or "aggressive" variant where skin involvement is usually absent but concomitant malignant hematological disorders (myelodysplastic and myeloproliferative syndromes and acute non-lymphocytic leukemias) are very common. Preliminary molecular biological studies of a few cases of malignant SMCD using the recently developed HUMARA assay have yielded evidence that the disease is monoclonal.

Animals↗
PubMed1996

Immunohistochemical localization of tissue inhibitor of metalloproteinases-2 (TIMP-2) in first trimester human placental decidua.

BACKGROUND: Matrix metalloproteinases have been shown to play an important role both in the invasive growth of malignant tumors and in human placentation. However, unlike tumor cell invasion, cytotrophoblast invasion is strictly controlled in its extent. Tissue inhibitors of metalloproteinases (TIMP) may play an important role in the modulation of cytotrophoblast growth into maternal tissue. STUDY DESIGN: We have undertaken an immunohistochemical study of the distribution of TIMP-2 in the decidua of first trimester human pregnancy. RESULTS: Moderate to strong staining for TIMP-2 was found in decidual stromal cells and the walls of blood vessels in all cases. No unequivocal staining of decidual leukocytes was seen. CONCLUSION: These findings suggest that TIMP-2 secretion in first trimester human decidua is confined to certain cell populations. Decidual stromal cells are probably an important source of TIMP and may contribute to the regulation of human cytotrophoblast invasion in vivo.

Decidua↗
PubMed1996

The distribution of tissue inhibitor of metalloproteinases-2 (TIMP-2) in the human placenta.

Matrix metalloproteinases (MMPs) secreted by human cytotrophoblasts are crucial for the invasion of the placental bed by these cells. The invasive growth of the trophoblast is similar to that of malignant tumours in many respects, but, unlike the latter, it is strictly controlled. Tissue inhibitors of metalloproteinases (TIMPs) have been postulated to play a role in the control of trophoblast invasion. In this immunohistochemical study, the distribution of TIMP-2 in the human placenta was investigated. In first trimester placenta, the cytotrophoblasts in columns exhibited strong cytoplasmic staining for TIMP-2. Villous cytotrophoblasts exhibited staining of moderate intensity with accentuation at the cell membrane, especially at the interfaces with the syncytiotrophoblast and the villous stroma. Staining of the cytoplasm and apical border of the syncytiotrophoblast was weak and focal. In term placenta, the few cytotrophoblasts present exhibited a staining pattern similar to that of the cytotrophoblasts in first trimester placenta, and there was marked linear staining of the syncytiotrophoblast at the interface with the stroma. Because it is the first trimester cytotrophoblast columns that invade the placental bed, the results demonstrate that the strongest immunoreactivity for TIMP-2 in the trophoblast is found in cells that are known to produce MMPs and exhibit an invasive growth pattern. These findings indicate that TIMP-2 may be involved in autoregulation of the invasive growth of the trophoblast.

Carrier Proteins↗
PubMed1996

A comparison of methods for heat-mediated antigen retrieval for immunoelectron microscopy: demonstration of cytokeratin No. 18 in normal and neoplastic hepatocytes.

Postembedding antigen retrieval is a well established technique for immunoelectron microscopy; however, many antigens cannot be detected without additional unmasking procedures. This study was undertaken to determine whether microwave oven heating, autoclaving, and pressurized boiling, which are well recognized methods of antigen retrieval for light microscopy, and simple boiling can also be used in electron microscopy. We investigated neoplastic and normal hepatocytes using a commercially available mouse monoclonal antibody against cytokeratin NO. 18 (CK 18). The tissue was fixed in paraformaldehyde/glutaraldehyde and embedded in Lowicryl K4M at -40 C. Ultrathin sections in various buffers were exposed to heat using one of four methods or to pronase at 37 C before incubation with the primary antibody. The secondary antibody was gold-labeled goat anti-mouse antibody. Sections that were not heat-treated remained unlabeled, but heat-treated sections showed immunoreactivity located mainly at the cytoplasmic periphery. Some of the gold particles lay in direct or loose association with intermediate filaments, some were seen in the area of desmosomes, and some did not appear related to any structures. No difference in immunostaining was found among the four methods of heat treatment. The citrate buffer, pH 6.0, and 10 mM EDTA, pH 8.0, generated the best labeling results.

Antigens↗
PubMed1996

Small epithelial cells and the histogenesis of hepatoblastoma. Electron microscopic, immunoelectron microscopic, and immunohistochemical findings.

The wide range of epithelial and mesenchymal lines of differentiation seen in hepatoblastoma suggests that this tumor derives from a pluripotent stem cell. To test this hypothesis, seven hepatoblastomas of various subtypes were investigated for the presence of cells with the features of the oval cells found during hepatocarcinogenesis in rodents that are thought to be closely related to hepatic stem cells. Because similar cells, referred to as "small cells," have been described in human liver disease with chronic ductular reaction, five liver biopsies from infants with biliary atresia were also investigated. The specimens were investigated by electron microscopy, immunoelectron microscopy, and immunostaining for cytokeratins 7, 8, 18, and 19. Small epithelial cells (SEC) corresponding to the oval cells of the rat and the "small cells" in humans were found in both biliary atresia and hepatoblastoma. These cells were oval and exhibited intercellular junctions, tonofilament bundles, and a biliary epithelium-type cytokeratin profile. SEC were found in small numbers in fetal hepatoblastoma and in moderate numbers in embryonal hepatoblastoma. In small cell hepatoblastoma, nearly all the tumor cells exhibited SEC-like ultrastructural features and a corresponding cytokeratin profile. Thus, cells exhibiting morphological and immunophenotypic features of hepatic stem cells are detectable in hepatoblastoma. Their numbers vary according to the subtype, reflecting the differing degrees of differentiation of the various subtypes, consistent with the theory propounded in the literature that embryonal and, with further differentiation, fetal tumor cells derive from precursor small cells. The findings support the hypothesis that hepatoblastoma derives from a pluripotent, probably entodermal or even less committed, stem cell.

Biliary Atresia↗
PubMed1996

Immunohistochemical and cytogenetic findings in malignant rhabdoid tumor.

BACKGROUND: The histogenesis of malignant rhabdoid tumor (RT) remains a matter of controversy. From published reports it appears that some extrarenal RT (ERRT) exhibit neural or neuroectodermal features. Systematic investigation of renal RT (RRT) for neural differentiation has not yet been published. In this study, two RRT and two ERRT were investigated by light and electron microscopy, immunocytochemistry, and cytogenetic analysis. RESULTS: All four cases exhibited similar morphology and a largely consistent immunohistochemical staining profile. Both tumor types showed immunoreactivity for various cytokeratins, epithelial membrane antigen (EMA), vimentin, neurofilaments, S100 protein, neuron specific enolase, Leu7, CD34, p53, MB2, MIC2, VS38c, laminin and fibronectin. Reactivity was usually confined to a small proportion of the tumor cells, especially in the case of antibodies against neurofilaments, NSE, S100 proteins Leu7, CD34 and p53. Only a few of the antibodies (anti-vimentin, MB2, MIC2, anti-EMA, and VS38c) stained the majority of the tumor cells. Chromosome analysis revealed a discrete aberration in 11p (most probably a paracentric inversion in 11p15) in the one RRT investigated. One ERRT had a normal karyotype, but the other one exhibited various structural abnormalities on chromosomes 18 and 22. CONCLUSIONS: The immunohistochemical investigations revealed many similarities between RRT and ERRT, and all four tumors investigated exhibited neuroectodermal differentiation. As far as histogenetic classification is concerned, our findings point in the direction of the group of tumors that includes Ewing's sarcoma and primitive neuroectodermal tumors.

Cytogenetics↗
PubMed1995

Expression of the p53 tumour suppressor gene in human placenta: an immunohistochemical study.

Since human trophoblast undergoes extensive proliferation and exhibits invasive growth comparable to that of a malignant tumour, human placenta at various different stages of gestation was investigated immunohistochemically with the monoclonal antibody Ab-6 for expression of the p53 tumour suppressor gene. p53 protein was detected in the nuclei of a few trophoblastic cells, almost all belonging to the cytotrophoblast and only very few to the syncytiotrophoblast, in nearly all specimens investigated (first trimester 10/10, second trimester 5/5, third trimester 4/5). First trimester trophoblast exhibited increased expression of p53 protein in the juxtastromal areas of cytotrophoblast cell islands and columns, that is, in areas where high proliferative activity and increased expression of the epidermal growth factor receptor have been described in the literature. Staining was also occasionally seen in trophoblast invading the myometrium. It is most likely that immunohistochemically detectable expression of p53 protein in the trophoblast is due not to mutation of the gene, as in malignant tumours, but rather to up-regulation of the p53 tumour suppressor gene, which could be a mechanism for controlling trophoblast proliferation.

Antibodies, Monoclonal↗
PubMed1995

Congenital epulis and granular cell tumor: a histologic and immunohistochemical study.

OBJECTIVES: Although it is now reasonably certain that granular cell tumors derive from Schwann cells, the histogenesis of congenital epulis, which is largely isomorphic with granular cell tumor, remains unclear. A study was undertaken to compare the immunophenotype of these tumors with particular emphasis on the expression of matrix proteins and macrophage markers because such information is not available in the literature. STUDY DESIGN: Four granular cell tumors and two congenital epulis were immunostained with a panel of 29 antibodies. Two congenital epulis and one granular cell tumor were investigated by electron microscopy, the latter also by immunoelectron microscopy. RESULTS: Many similarities in immunostaining were found, for example, both tumor types were CD68+, Ki-M1P+, lysozyme-, vimentin+, fibronectin+, laminin+, lectin PHAE+, and lectin WGA+. However, differences were also noted, for example, granular cell tumor was always S100 protein+, but only one congenital epulis case was reactive (weak reactivity after microwave treatment), and staining with the proliferation markers anti-proliferating cell nuclear antigen and MIB 1 was found only in congenital epulis. Both tumor types exhibited pericellular and diffuse cytoplasmic staining for fibronectin and laminin. CONCLUSIONS: The hypothesis that congenital epulis and granular cell tumor would exhibit similar reactivity for macrophage markers was confirmed: both were reactive with anti-CD68 and Ki-M1P and nonreactive with MAC387, anti-lysozyme, and 3A5. Intracytoplasmic staining for fibronectin and laminin, which has not been described previously in these tumors, appears to be a characteristic feature common to both tumors. This finding suggests that there could be a disturbance of synthesis and secretion of extracellular matrix proteins or a derangement of their receptor systems. This theory could be supported by the finding of intracytoplasmic CD49e-positive material in two cases.

Antibodies, Monoclonal↗
PubMed1995

[Leiomyosarcoma of the temporal bone].

This is a report on a patient of 74 years of age presenting with ear pain and bleeding granulations on his tympanic membrane. X-ray of the mastoid revealed partial destruction of the bone structures and reduced pneumatisation. A tumour that was mainly located in the temporal bone was surgically removed and proved to be a leiomyosarcoma. This is the first case of a leiomyosarcoma of the temporal bone to be described. Differential diagnosis and therapy of this tumour are discussed.

Actins↗
PubMed1995

[Liposarcoma in the head-neck area].

Between 1977 and 1992 four patients with liposarcomas of the head and neck region were treated and regularly reexamined at the ENT department of the University of Tubingen. Our patients were aged 19, 64, 66, and 73 years at primary diagnosis. Three patients were female and one was male. The tumors were located in cheek/parotid gland, the neck, the tracheoesophageal region and larynx/hypopharynx. In three patients complete primary resection was planned. In three cases further surgery was necessary due to recurrences. Two patients are free of tumor for seven and nine years, respectively. One patient was irradiated with 70 Gy four years after primary surgery since she had developed an unresectable recurrence. She died eleven years later aged 79 without residual liposarcoma (autopsy). One patient aged 76 rejected a radical resection and underwent a functional tumor reduction and is alive in fairly good condition. Histologically we found one myxoid and three well-differentiated liposarcomas. Metastatic spread was not observed. Wide tumor excision is the therapy of choice. Unresectable tumors can be irradiated successfully (up to 70 Gy are necessary). Representative studies on the value of chemotherapy have not yet been presented. The main factor in clinical behavior and prognosis of this rare tumor is the histological subtype. While well-differentiated and myxoid liposarcomas show almost no metastasis and good prognosis, the pleomorphic and round cell type do metastasis, recur more often, and have a significantly worse prognosis.

Adult↗
PubMed1995

Immunoreactivity of sinusoids in hepatoblastoma: an immunohistochemical study using lectin UEA-1 and antibodies against endothelium-associated antigens, including CD34.

Sinusoids are found not only in the normal liver but also in certain liver tumours, including hepatoblastoma, the most common malignant liver tumour in childhood. In this study, sinusoids in 12 hepatoblastomas, of various subtypes, and in normal liver were investigated with UEA-1 and antibodies against von Willebrand's factor, CD31 and CD34 to detect differences of possible diagnostic significance. In the normal liver, staining of sinusoids was seen with all these markers, but it was focal and confined to a few sinusoids near the portal tracts. In hepatoblastoma, the endothelial markers reacted with the sinusoids to varying extents. UEA-1 and anti-CD34 usually stained the majority of these vessels, anti-CD34 staining greater numbers of sinusoids and with greater intensity. Immunostaining revealed that both number and spatial organization of sinusoids in hepatoblastoma are dependent on the subtype. In addition to staining of endothelium, one of the two small cell hepatoblastomas exhibited strong immunoreactivity of the tumour cells for CD34. These findings show that the marked difference in sinusoidal immunoreactivity for CD34 between normal liver and hepatoblastoma could be useful for discriminating between non-neoplastic liver tissue and highly differentiated fetal hepatoblastoma. Our findings also show that small cell hepatoblastoma, in addition to acute leukaemia, should be considered when immunoreactivity for CD34 is found in small round and blue cell tumours in childhood.

Antigens, CD↗
PubMed1995

Flow cytometric evaluation of nuclear DNA content in hepatoblastoma: further evidence for the inhomogeneity of the different subtypes.

The DNA ploidy pattern of nine hepatoblastomas and three normal liver specimens was investigated by flow cytometry. Areas of unlike differentiation in the same tumor were investigated separately. Normal liver tissue and the fetal subtype were always diploid. Aneuploidy was found in the embryonal subtype. The one case of small cell tumor was also diploid. When the fetal and embryonal areas of the same tumor were analyzed together, there was always an aneuploid peak in the histogram. There are obvious differences in DNA ploidy among the various hepatoblastoma subtypes. Differences in methods used, including the failure in some studies to evaluate areas of unlike differentiation in the same tumor separately, probably account to some extent for the conflicting results of previously reported studies. When flow cytometric analysis of the DNA content of a hepatoblastoma is performed, it is important to ensure that the various types of differentiation in the tumor are represented adequately in the material investigated, especially when conclusions about the prognosis are to be based on these findings.

Aneuploidy↗
PubMed1995

Evidence for a lymphotropic nature of circulating plasmacytoid monocytes: findings from a case of CD56+ chronic myelomonocytic leukemia.

Because the cells previously designated plasmacytoid T cells share major immunophenotypic features with cells of the mononuclear-phagocyte system, they have been re-named and are now known as plasmacytoid monocytes (PM). We describe a unique case of chronic myelomonocytic leukemia with circulating PM. The patient, a 48-year-old man, presented initially with refractory anemia. Four years later his general condition deteriorated, accompanied by an increase in leukocytes to 200,000/microliters blood. The bone marrow histology was interpreted as compatible with a diagnosis of chronic myelomonocytic leukemia. Two months before he died, the patient developed generalized lymphadenopathy clinically simulating malignant lymphoma. Histologic examination of an axillary lymph node revealed diffuse infiltration by PM. The PM in the lymph node and some circulating cells closely resembling PM expressed L-selectin, a finding that could be interpreted as a morphologic correlate of their marked lymphotropism. The detection of large numbers of CD56/CD33 double-positive circulating blast cells by FACS analysis strongly supported the diagnosis of a leukemia of myelogenous origin. The patient died of tumor cachexia. Autopsy revealed widespread leukemic infiltrates (always containing clusters of PM) in bone marrow, spleen, liver, lymph nodes, and mucosa-associated lymphoid tissue of the oropharynx. The final diagnosis was one of chronic myelomonocytic leukemia with marked lymphotropism and partial differentiation towards PM. We consider that the rare instances of a hematologic tumor with differentiation towards PM should be classified amongst the myelogenous leukemias.

Antigens, CD↗