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D Katenkamp

Publications and source records attributed to D Katenkamp.

At least 19 recordsLinked to original sources

Solitary fibrous tumour: clinicopathological, immunohistochemical, and ultrastructural analysis of 12 cases arising in soft tissues, nasal cavity and nasopharynx, urinary bladder and prostate.

The clinicopathological features of 12 extraserosal solitary fibrous tumours (SFT) are described. The age of the patients ranged from 18 to 72 years (mean: 48.2 years; median: 54 years); 5 were female patients. Seven lesions arose in soft tissue (5 in perifascial, and 1 each in subcutaneous and intramuscular tissues). They were situated in the groin (2 cases) and the neck, right buttock, left scapula, upper arm, and anterior abdominal wall (1 case each). One polypoid lesion was seen in in the nasal cavity and 1 in the nasopharynx; 2 neoplasms arose in the urinary bladder and 1 was located in the prostate and periprostatic tissue. Nine lesions were excised; in 1 patient wide excision was performed and in 2 patients, transurethral resection. Limited follow-up of 3 cases revealed a benign clinical course. The size of the neoplasms ranged from 1.7 cm to 20.0 cm (mean: 5.4 cm; median: 3.5 cm). Histologically, the neoplasms were well circumscribed and composed of cytologically bland spindle cells arranged without an obvious pattern; focally storiform or fascicular growth patterns were seen. Tumour cells were separated by thick bands of collagen demonstrating foci of keloid-like hyalinization. Prominent vascularity showing a haemangiopericytoma-like vascular pattern and vessels with thick, hyalinized vessel walls were seen in all cases. Increased mitotic activity was noted in 2 soft tissue cases (4-6 mitoses in 10 high-power fields); the other cases showed fewer than 2 mitotic figures in 10 highpower fields. Immunohistochemically, all cases tested stained positively for vimentin, CD34 and CD99, and 2 cases showed focal myofibroblastic differentiation. Two cases examined ultrastructurally showed a fibroblastic phenotype; focally pinocytic vesicles and microfilaments were identified. SFT represents a distinct neoplasm that should be included in the differential diagnosis of spindle-cell neoplasms in soft tissue, nasal cavity and nasopharynx, urinary bladder, and prostate. Strict diagnostic criteria are necessary to avoid overdiagnosis or confusion with more aggressive neoplasms in these locations.

Adolescent

Quantitative evaluation of apoptosis and proliferation in renal cell carcinoma. Correlation to tumor subtype, cytological grade according to thoenes-classification and the occurrence of metastasis.

To analyse growth characteristics of human renal cell tumors, 66 renal cell carcinomas and one oncocytoma were investigated concerning the proliferative activity by immunohistochemical demonstration of the Ki-67 antigen (clone MIB1) and the apoptotic rate using the terminal deoxynucleotidyl-transferase mediated dUTP-fluorescin nick end labelling (TUNEL) method. The TUNEL method indicates DNA double strand breaks considered as a hallmark of programmed cell death (apoptosis). Apoptotic cells were observed in 57 of 67 cases. The apoptotic rate (percentage of stained tumor cells) varied from 0% to 54.1%. GI carcinomas possessed a statistically significant higher apoptotic rate than GII/GIII carcinomas. The proliferation index (percentage of Ki-67 labelled cells) ranged from 0.09% to 22.3%. The well differentiated carcinomas (GI) showed statistically lower proliferative activity than moderate and poorly differentiated carcinomas (GII/GII). The clear cell variant of renal cell carcinoma expressed a higher apoptotic rate than the chromophilic variant. A statistical correlation between apoptosis/proliferation and occurrence of metastasis could not be established. In progression from well to less differentiated renal cell carcinoma the decrease of apoptotic rate, as well as the increase of the proliferative activity, contributes to a rapid tumor growth.

Adenocarcinoma, Clear Cell

Epithelioid hemangioendothelioma of skin and soft tissues: clinicopathologic and immunohistochemical study of 30 cases.

Epithelioid hemangioendothelioma of soft tissues (EHE) represents a distinct entity with an unpredictable clinical course. We analyzed the clinicopathologic and immunohistochemical features in a series of 30 patients. Patient age range was 16-74 years (median 50); 18 of 30 patients were female. Eight tumors arose in the lower and two in the upper extremities, seven on the trunk, five each in the head/ neck and anogenital regions, two in the mediastinum, and one in the abdomen. Seventeen neoplasms were located in deep soft tissues, nine were subcutaneous or perifascial, and four were dermal; size ranged from 0.4 to 10 cm; in 11 cases the tumor was > 5 cm. Tumors with an infiltrative growth pattern were more common than entirely circumscribed lesions. The tumors were composed histologically of short strands, cords, or small clusters of epithelioid, round, to slightly spindled endothelial cells that formed at least focally, intracellular lumina and were set in a frequently myxohyaline stroma. Thirteen of 30 lesions showed angiocentric growth, which was occlusive in many cases. Immunohistochemically, all cases tested were positive for at least one endothelial marker (CD31, CD34, factor VIII, Ulex europaeus), six of 23 (26%) were positive for cytokeratin, and five of 11 (45%) were positive for alpha-smooth muscle actin. Median follow-up of 36 months (range 2-96) in 24 cases showed local recurrence in three cases and systemic metastases in five cases (21%); four patients (17%) died of tumor. Although more aggressive histologic features (striking nuclear atypia in eight cases, numerous spindled cells in 10, more than two mitoses per 10 high-power fields in nine, and small, more solid angiosarcomalike foci in four cases) tended to be related to poor clinical outcome, there was no clear correlation. Two metastasizing cases showed no histologically atypical features whatever. We suggest that EHE of soft tissue is better regarded as a fully malignant, rather than borderline, vascular neoplasm, albeit the prognosis is better than in conventional angiosarcoma.

Adolescent

Limiting dilution analysis of the frequency of autoreactive lymph node cells isolated from mice with antigen-induced arthritis.

Antigen-induced arthritis (AIA) in mice occurs after the single injection of methylated bovine serum albumin (mBSA) into the knee joint of animals preimmunized with the same antigen in complete Freund's adjuvant. A short acute reaction is followed by a chronic inflammation which shows similar histological features to human rheumatoid arthritis. The mechanisms leading to the chronicity of arthritis are not yet clear. Previous data suggest that autoimmune responses to cartilage components contribute to the persistence of arthritis. In the present study we estimate the frequency of autoreactive cells in the draining lymph nodes of arthritic mice by means of limiting dilution analysis. Graded concentrations of lymph node cells were stimulated for 7 days with type II collagen (CII) or cartilage proteoglycans (PG) in the presence of irradiated syngeneic feeder cells, and the frequency of responding cells was calculated. In the draining lymph nodes of immunized mice without arthritis induction, the frequency of CII reactive lymph node cells ranged from 1/41,182 to 1/57,424 whereas only 1 out of 3 experiments revealed a detectable frequency of PG reactive cells (1/136,128). For comparison, no CII or PG reactive cells were detected in the lymph nodes of normal mice. Intra-articular challenge of immunized mice with mBSA resulted in chronic destructive arthritis and caused a significant increase in the frequencies of CII and PG reactive lymph node cells (1/12,776 to 1/24,611 and 1/79,964 to 1/93,075, respectively). When using incomplete Freund's adjuvant for immunization, a comparable acute arthritis developed after the intra-articular injection of antigen, but the transition into the chronic stage was missing. The frequencies of autoreactive cells in the lymph nodes of these animals were below the level of detection and were judged to be below 1/150,000. The results suggest that autoimmune reactions against cartilage constituents might contribute to the perpetuation of joint inflammation, and that the mycobacteria in the complete Freund's adjuvant play an essential role in this process.

Animals

Molecular variants of fibronectin and laminin: structure, physiological occurrence and histopathological aspects.

This review deals with biological and pathological aspects of various isoforms of the matrix molecules fibronectin and laminin. They are generated by different molecular mechanisms: ED-A+ and ED-B+ fibronectin by alternative splicing of pre mRNA, de novo-glycosylated fibronectin by alternative post-translational O-linked glycosylation of the IIICS region, and the laminin isoforms by exchange of single chains of the heterotrimeric molecule. In contrast to the "common" fibronectin, the distribution of ED-B+ and de novo-glycosylated fibronectin is restricted to embryonic tissues; they subsequently reappear in granulation tissue, in fibrosing processes and in tumour stroma. The expression of these so-called oncofetal fibronectins is stimulated by growth factors (TGF beta). The association of the ED-B+ fibronectin with proliferative activity and newly formed vessels identifies this fibronectin variant as a marker of cellular activity in the process of fibrosis and as a suitable agent for the evaluation of tumour angioneogenesis. Initial results suggest a correlation between the amount of ED-B+ and de novo-glycosylated fibronectin in tumour stroma and the behaviour of carcinomas with regard to their invasiveness and propensity for metastatic dissemination. The current nomenclature of the laminin molecule family is presented. The laminin chain constitution of basement membranes switches from embryonic or proliferatively active to adult terminally differentiated tissues [disappearance of the laminin beta 2 (s) chain] and depends on the tissue type. The discrepancy between the loss of basement membranes (multiple basement membrane defects) in carcinomas and the recently reported increased laminin chain synthesis in these tumours may be explained by abundant laminin chain deposition outside the basement membrane in the carcinoma invasion front, possibly associated with enhanced adhesion of budding tumour cells.

Animals

Immunomodulation of rat antigen-induced arthritis by leflunomide alone and in combination with cyclosporin A.

The effects of the new immunomodulating isoxazol derivative leflunomide, in comparison with cyclosporin A, on established antigen-induced arthritis in rats as well as serum antibody levels were determined. When treatment with leflunomide, at concentrations from 2.5 to 10 mg/kg/d, was started on day 3 of arthritis, the acute and chronic phases of arthritis were effectively inhibited. This was demonstrated by decreased joint swelling and reduced histopathological arthritis score at the end of experiment (day 26). Furthermore, the treatment resulted in a significantly reduced level of serum antibodies to the matrix components collagen type I, type II and proteoglycans. Neither leflunomide nor cyclosporin A, at doses of 1 mg/kg/d, had an effect on the severity of arthritis and antibody levels. However, when both drugs were used together, at these non-effective doses, the histopathological score of chronic arthritis was significantly reduced. The results of our experiments demonstrate that leflunomide has a strong suppressive effect on both acute and chronic phases of antigen-induced arthritis and formation of autoantibodies in rats. Furthermore, orally administered doses of leflunomide were as effective as doses of cyclosporin A given intraperitoneally. The combination of sub-effective doses of leflunomide and cyclosporin A resulted in significant inhibition of chronic arthritis.

Animals

[Low malignancy myxofibrosarcoma versus low malignancy fibromyxoid sarcoma. Distinct entities with similar names but different clinical course].

Low-grade myxofibrosarcoma (MFS) and low-grade fibromyxoid sarcoma (FMS) are two distinct entities in the spectrum of myxoid mesenchymal sarcomas with fibroblastic differentiation. Low-grade MFS is seen often in the extremities of elderly patients, subcutaneously more frequent than in deep soft tissues, whereas the majority of cases of low-grade FMS occur in young to middle-aged adults, commonly in deep soft tissues of the shoulder region, the extremities and the trunk. Histologically, low-grade MFS shows a multinodular growth pattern and is composed of round or polygonal tumour cells mixed with elongated, curvilinear, thin-walled blood vessels in a myxoid matrix. The tumour cell nuclei in low-grade MFS display at least moderate nuclear pleomorphism and hyperchromasia. Low-grade FMS, however, is composed of bland fusiform tumour cells arranged in a whorled or swirling pattern, or occasionally more linear, and set characteristically in an alternating fibrous and myxoid stroma. Low-grade MFS recurs frequently but has a very low metastatic potential, whereas low-grade FMS is characterised by an indolent but ultimately malignant clinical course with metastases in more than half of the cases, which underlines the importance of distinguishing between the two entities.

Adult

[CD34 detection--an immunohistochemical contribution to differential diagnosis of soft tissue tumors].

CD34 is a myeloid progenitor cel antigen and present in endothelial cells and almost all vascular lesions. Additionally, CD34 has been described in numerous fibroblast-like cells and different mesenchymal tumours. The immunohistochemical evidence of CD34, however, may be of importance in the differential diagnosis of benign and malignant soft tissue lesions, if clinicopathological features and other immunohistochemical markers are regarded properly. We studied the CD34 immunopositivity of solitary fibrous tumour at different sites (11 out of 11 tumours tested stained positive), dermatofibrosarcoma protuberans (15 out of 18 stained positive), and gastrointestinal stromal tumour (15 out of 15 stained positive), and discuss the significance of these results in differential diagnosis to morphologically comparable soft tissue lesions.

Adolescent

[Infantile rhabdomyofibrosarcoma. An aggressive tumor in the spectrum of spindle cell tumors in childhood].

We report a case of an intrathoracic, extrapleural, infantile rhabdomyofibrosarcoma in a 4-year-old boy. Histologically, the primary lesion showed extensive hyalinization and stroma sclerosis and was composed of relatively uniform spindle-shaped, at least focally rather polygonal tumour cells with scattered intracytoplasmatic globoid inclusions. Although chemo- and radiotherapy was given postoperatively, local recurrences and metastases in the lung and thymus have developed; the patient died of tumour disease 3 years later. Recurrences and metastases showed features of tumour progression with higher cellularity and increased mitotic activity. Immunohistochemically, the tumour cells stained strongly positive for vimentin, desmin, and muscle-specific actin, and at least focally for MyoD1; the tumour did not stain for alpha-smooth muscle actin, neural and epithelial markers, or CD34 and CD31. The differential diagnosis of these aggressive tumours in the spectrum of spindle-cell lesions in early childhood is discussed.

Biomarkers, Tumor

Reduced formamide content and hybridization temperature results in increased non-radioactive mRNA in situ hybridization signals.

To define conditions for highly sensitive non-radioactive mRNA in situ hybridization on cryostat sections the influence of decreased formamide content and hybridization temperature was studied. The examination was performed on fibromatosis nodules of palmar fibromatosis visualizing the beta actin mRNA of myofibroblasts. The results show that a decrease in formamide content and hybridization temperature is able to enhance the sensitivity of mRNA detection applicating digoxigenin labelled DNA oligodeoxynucleotide. The best hybridization signal could be obtained under formamide-free conditions. In conclusion, a simplified sensitive formamide-free mRNA in situ hybridization protocol using oligonucleotide probes on human tissue cryostat sections is presented. The negative formamide effect is seen as a result of the chemical interaction of formamide with nucleic acid strands. An omission of formamide is suggested if the target as well as the probe are single stranded.

Actins

Matrix remodelling in dilated cardiomyopathy entails the occurrence of oncofetal fibronectin molecular variants.

OBJECTIVES: To investigate whether disturbance of the cellular homoeostasis and integrity of cardiomyocytes in dilated cardiomyopathy (DCM) is accompanied by alterations in cell-matrix relations as indicated by changes in the deposition of fibronectin (FN) isoforms. DESIGN: Tissue from a case series of patients with DCM was investigated by immunohistochemistry with antibodies against FN (all variants, clone IST4), ED-A+ FN (clone IST9), ED-B+ FN (clone BC1), and oncofetal glycosylated FN (clone 5C10). The sites of de novo synthesis of FN were demonstrated by means of non-radioactive RNA in situ hybridisation (ISH) with biotinylated FN cDNA fragments as the probe. SETTING: University hospital. PATIENTS: Samples from 10 patients with clinical criteria and histological diagnosis of DCM and from 3 individuals with normal hearts. INTERVENTIONS: Samples were obtained by right ventricular endomyocardial biopsy. MAIN OUTCOME MEASURE: Distribution of oncofetal FN variants in DCM hearts. RESULTS: Immunostaining of FN (IST4, all variants) showed a coarse interstitial network in normal and diseased myocardium. ED-A+ FN was deposited as fine interstitial spots in normal myocardium and in DCM samples. Immunostaining for oncofetal glycosylated FN and ED-B+ FN was not seen in normal adult myocardium, whereas myocardium from DCM patients showed focal and delicate staining in the interstitium. RNA ISH showed that these deposits resulted from local FN synthesis. CONCLUSION: The results accord with de novo expression of oncofetal FN variants in hearts from patients with DCM. The oncofetal FN variants may serve as disease markers in myocardium affected by DCM.

Adult

Adoptive transfer of susceptibility to antigen-induced arthritis into severe combined immunodeficient (SCID) mice: role of CD4+ and CD8+ T cells.

Antigen-induced arthritis (AIA) in mice occurs after immunization and a subsequent intra-articular injection with methylated bovine serum albumin (mBSA). The role of T lymphocytes in the adoptive transfer of susceptibility to AIA into SCID mice was investigated. Pooled spleen and lymph node cells from immunized syngeneic or allogeneic donor mice, isolated either before or after the induction of arthritis, could transfer the capacity both to develop arthritis and to produce antibodies to mBSA, collagen type II and cartilage proteoglycans into SCID mice. The intra-articular injection of mBSA in responder animals, immediately after the cell transfer, resulted in a chronic arthritis in the induced joint. The histologic examination revealed synovial hyperplasia, mononuclear infiltration of the synovial membrane, exudation of polymorphonuclear leucocytes into the joint space, and chondrocyte death. The depletion of CD4+ T cells before transfer prevented the manifestation of arthritis in SCID mice, with a concomitant decrease in antibody levels to mBSA, collagen type II and cartilage proteoglycans. In contrast, removal of CD8+ T cells did not significantly affect the transfer of arthritis into SCID mice. The results demonstrate an essential role of CD4+ T cells in the pathogenesis of AIA, whereas CD8+ T cells do not seem to be required for the induction and perpetuation of this disease.

Adoptive Transfer

[Cyto- and molecular genetic studies of renal cell carcinoma with special reference to multifocal carcinoma lesions].

In 86 consecutive radical nephrectomies we found in 12 kidneys (13.8%) a total of 17 multicentric foci of carcinoma. Beside the usual histopathological investigations we performed in seven secondary tumors further cyto-and molecular genetic analyses. The structural and/or numerical chromosome aberrations in the small secondary tumors were similar to the changes in the main tumors. We conclude that these foci have malignant potential. In eight of these results and the multicentricity that was found, we continue to recommend elective radical nephrectomy in renal cell carcinoma.

Aged

[Ectopic hamartomatous thymoma. Case report with special reference to differential diagnosis].

We report the case of an ectopic hamartomatous thymoma in a 56-year-old male patient. The lesion arose subcutaneously in the supraclavicular region. Histologically, the well-circumscribed but unencapsulated tumour was composed of uniform fusiform tumour cells. In addition, mature fatty tissue, scattered T-lymphocytes, and an epithelial and a myoepithelial tumour cell component were found. The epithelial differentiation of the spindle cell tumour component was confirmed immunohistochemically and by electron microscopy. Ectopic hamartomatous thymoma has to be distinguished from ectopic cervical thymoma, thymolipoma, ectopic salivary tissue, teratoma, peripheral nerve sheath tumours, malignant epithelial tumours with thymus-like differentiation, biphasic synovial sarcoma, and skin adnexal tumours.

Biomarkers, Tumor