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Biomedical subjects

L D Leder

Publications and source records attributed to L D Leder.

At least 19 recordsLinked to original sources

Clinical and histological features retain their prognostic impact under interferon therapy of CML: a pilot study.

In 55 patients with Ph1+ CML under interferon (IFN) monotherapy, an immunohistochemical and morphometric study on pretreatment bone marrow biopsies was performed to evaluate the prognostic impact of clinical as well as histological disease features. For identification of megakaryocytes we used the PAS stain and CD61 to calculate the subfraction of precursors (pro- and megakaryoblasts). Demonstration of macrophages and their different subsets was carried out by PG-M1 (CD68) and the GSA-1 lectin. The erythroid precursors were stained by Ret40f (anti-glycophorin C). Density of argyrophilic (reticulin plus collagen) fibers was determined by applying Gomori's silver impregnation method. Clinical variables like state of hematological response to IFN administration, age, spleen and liver size, myeloblasts plus promyelocytes, basophils as well as basophils and eosinophils exerted a predictive capacity by univariate statistical analysis. However, when entering these factors into previously published risk models, i.e., the so-called Sokal score and its modifications, to assess subgroups with different survival patterns or relative risk groups, a clear-cut discrimination was not feasible. Bone marrow features of prognostic value consisted of megakaryocytes and their precursors, fibers, and pro- and erythroblasts. Only when including histological variables into a formerly reported Cox model, could a significant separation of patients into the different categories or relative risk groups be computated. In conclusion, the present data emphasize the prognostic impact of histological parameters to be considered in all clinical trials on CML.

Adult

The impact of interferon versus busulfan therapy on the reticulin stain-measured fibrosis in CML--a comparative morphometric study on sequential trephine biopsies.

To evaluate treatment-related changes of the reticulin stain-measured fibrosis in Ph(1+)-CML, a clinicopathological study was performed on sequential trephine biopsies of the bone marrow following either interferon (IFN) or busulfan (BU) monotherapy. Using the monoclonal antibody CD61 for the identification of megakaryopoiesis and Gomori's silver impregnation method, number of megakaryocytes and density of argyrophilic (reticulin and collagen) fibers were determined by morphometry. We studied specimens from 26 patients with IFN-alpha 2b (including nine patients with additional IFN gamma) therapy and from 23 patients who had received BU. In both groups, repeated bone marrow biopsies (total 125) revealed a significant increase in the fiber content, as well as in the number of megakaryocytes during treatment. To assess the dynamics of myelofibrosis more precisely, computation of differences in the degree of fiber density between the first and last examination was carried out. Regarding the considerable variations in the biopsy intervals, a so-called myelofibrosis progression index (MPI) was calculated. Following this rationale, we were able to demonstrate that, in comparison to the BU-group, speed of progression of bone marrow fibrosis was significantly increased in CML patients treated with IFN. Preliminary statistical analysis indicated a relationship between myelofibrosis on admission, which was always associated with increased growth of megakaryocytes, and the MPI with survival. Even when these parameters were regarded, prognosis was significantly more favorable in the IFN-treated patients. The failure of IFN and BU to inhibit the evolution of myelofibrosis may be related to several conversely acting pathomechanisms. Among others, the inability of both therapeutic agents to reduce the number of megakaryocytes more effectively should be taken into consideration.

Adolescent

T-cell-rich B-cell lymphoma and lymphocyte-predominant Hodgkin's disease: two closely related entities?

T-cell-rich B-cell lymphoma (TCRBCL) is a recently described variant of non-Hodgkin's lymphoma. It may arise de novo or secondary to follicular lymphoma and large B-cell lymphoma. We present here seven cases of TCRBCL to emphasize a peculiar relationship to lymphocyte-predominant Hodgkin's disease. Morphologically, the neoplastic populations of all TCRBCLs, in addition to centroblast-like and immunoblast-like cells, comprised a few L+H-like elements. These neoplastic cells were all regularly scattered in a majority of reactive small T-lymphocytes as well as histiocytes. Moreover, tumour cells of TCRBCL, including the L+H-like elements of TCRBCL, expressed LCA and L26 but did not stain for Leu-M1 and BerH2, as is the case with the Reed-Sternberg cell L+H variant of lymphocyte-predominant Hodgkin's disease. Furthermore, the L26 immunoreaction in one of the cases, which otherwise presented as typical TCRBCL, disclosed a small subcapsular area resembling nodular paragranuloma because some few foci consisting of mature B lymphocytes with occasional L+H-like elements were seen. This also holds true for a second of the TCRBCLs presented that obviously coexisted with recurrent Hodgkin's paragranuloma 10 years after the primary manifestation. These findings indicate a close connection between TCRBCL and lymphocyte-rich Hodgkin's disease, and it may even be speculated as to whether TCRBCL represents merely a phenotypically different manifestation of this Hodgkin's subtype. Although the data presented here will not provide sufficient proof of this hypothesis, it seems clear that the nosology of TCRBCL in the context of current lymphoma classifications requires further elucidation.

Adult

Deep venous thrombosis and pulmonary artery embolism in high-grade non Hodgkin's lymphoma: incidence, causes and prognostic relevance.

To analyse incidence, risk factors, causes and prognostic significance of venous thromboembolism (VTE) in high-grade non-Hodgkin's lymphoma (HG-NHL) a prospective clinical trial (N = 593), also undertaken to analyse other aspects of HG-NHL, a study of haemostasis (N = 25) and a post-mortem analysis (N = 70) were performed. Clinical analysis documented a 6.6% incidence of VTE, and 77% of all cases occurred before or within the first 3 months of chemotherapy. Ann Arbor stage IV and B-mediastinal clear cell histology were risk factors for VTE, while rapid changes in tumour load or application of consolidation chemotherapy were not. Vessel compression by HG-NHL was the leading cause of VTE, whereas a significant (paraneoplastic or chemotherapy-induced) thrombophilic state was not disclosed by haemostatic tests. While VTE-related fatality was found to be low in the clinical trial (1.7%) and at necropsy (8.5%), the occurrence of VTE was associated with an unsatisfactory response of HG-NHL to chemotherapy and a high incidence of treatment-related mortality due to diffuse alveolitis. Thus, fatal VTE in HG-NHL is rare, but VTE is associated with an unfavourable clinical course of HG-NHL.

Adolescent

Multiple myeloma with bone marrow biopsy features simulating concomitant chronic idiopathic myelofibrosis.

Multiple myelomas occasionally exhibit bone marrow lesions simulating a concomitant chronic idiopathic myelofibrosis. In the present study, trephine biopsy histologies of such "myelofibrotic" myelomas are described and compared to those from a case of true chronic idiopathic myelofibrosis which developed in the course of chronic lymphocytic leukaemia. "Myelofibrotic" myeloma are characterized by osteosclerosis, marrow fibrosis and focal megakaryocytic hyperplasia in the presence of plasma cell infiltration of the bone marrow. These myelomas are to be distinguished from the more commonly occurring multiple myeloma with simple marrow fibrosis and/or osteosclerosis. Furthermore, "myelofibrotic" myelomas are not identical to myelomas coexisting with true chronic idiopathic myelofibrosis, a condition which would appear to be extremely rare and should only be diagnosed if focal megakaryocytic hyperplasia with atypia can be unequivocally demonstrated. Avoidance of misinterpretation of "myelofibrotic" myeloma requires a knowledge of these different myeloma variants.

Adult

Well-differentiated (oncocytoid) neuroendocrine carcinoma of the larynx with multiple skin metastases: a brief report.

A 63-year-old woman presented with a history of increasing dysphagia of about two weeks duration. Laryngoscopy revealed a nonulcerated supraglottic epitheliomatous lesion that morphologically appeared well-differentiated and distinctly oncocytoid. Although the tumour lacked any criteria for malignancy such as cellular atypia, pleomorphism or necroses, it recurred twice after primary surgery and later gave rise to multiple painful skin metastases. The diagnosis of an oncocytoid differentiated neuroendocrine carcinoma of the larynx (laryngeal carcinoid) was made. Misinterpretation of laryngeal carcinoids is common, but can be avoided if one is familiar with this rare variant of laryngeal neoplasms.

Carcinoid Tumor

Mucoid cytoplasmic inclusions in urothelial carcinomas.

To date, mucoid cytoplasmic inclusions in urothelial carcinomas have rarely been noted. However, we were impressed by the fact that these corpuscles are readily detectable in numerous urothelial neoplasms. Therefore, a histologic analysis of 100 cases of urothelial carcinomas was performed. Overall, 37 cases revealed periodic acid-Schiff-positive cytoplasmic inclusions. These were observed in 14% of grade 1, 49% of grade 2, and 63% of grade 3 carcinomas. The inclusions were histochemically, immunohistochemically, and ultrastructurally identified as cytoplasmic deposits of mucoid materials. Two types of deposits, condensed and noncondensed, could be distinguished. The demonstration of mucoid deposits in otherwise poorly differentiated metastatic carcinomas may be of some differential diagnostic importance insofar as urothelial carcinoma has to be considered as the possible primary tumor.

Carcinoma, Transitional Cell

Mast cell frequency in soft tissue tumors. Relation to type and grade of malignancy.

A high content of mast cells (MC) is considered characteristic of neurofibromas but not of malignant schwannomas and neurilemmomas. We examined the extent and reliability of this finding by counting MC in 61 peripheral nerve sheath tumors and in 103 non-neurogenic soft tissue sarcomas. We furthermore investigated correlations between the amount of MC and various features of the tumors (e.g. grades of malignancy). Neurofibromas had very high mast cell counts. However, this result only applied to about 70% of these tumors. Malignant schwannomas, malignant fibrous histiocytomas and leiomyosarcomas had remarkably high median values of MC counts with a wide dispersion within the histological groups. Synovial sarcomas were the only group that contained MC in every case, though often in small numbers. In univariate analyses the number of MC was negatively correlated to grades of malignancy, cellularity and mitotic activity of the sarcomas and tended to correlate positively to the amount of myxoid and collagenous connective tissue and lymphocytic infiltrates. Multiple linear regression analysis revealed a significant correlation to the grade of malignancy and the amount of connective tissue.

Cell Count

[Angioimmunoblastic lymphadenopathy (AILD): histology and survival time].

In order to identify histological and immunohistochemical criteria of prognostic value in AILD 40 lymph nodes with typical and 15 cases with incomplete features were semiquantitatively analyzed. Their expression were correlated with survival data of all patients. Significant prognostic value could be detected for following parameters: mitoses, immunoblasts, CD 30-positive blasts, multinuclear tumor cells and eosinophilic granulocytes. However residual lymph node structures, venules, PAS-positive material, and reticulum cells did not correlate with survival data. The short median survival time does not justify AILD grouping as low grade malignant lymphoma.

Antigens, CD

[Morphological and immunohistochemical findings on the frequency of intranuclear immunoglobulin inclusions (Dutcher bodies) in malignant B-cell lymphomas].

318 cases of 682 malignant B-cell lymphomas reacted positive for cIg. 66 of them showed Dutcher bodies (DB). DB were found in about 22% of plasmacytomas, 17% of immunocytomas, and in 7.5% of follicular lymphomas and polymorphic centroblastomas, respectively. Regarding only the cIg-positive cases, DB occurred in about 27% of immunocytomas, 20% of follicular lymphomas and 18% of polymorphic centroblastomas. A single case of prolymphocytic leukaemia, centrocytoma, monomorphic centroblastoma, and immunoblastoma each showed also DB. Usually, DB-positive plasmacytomas showed kappa, alpha, and J-chains. The remaining lymphomas mostly expressed kappa, my, and J-chains. In conclusion Dutcher bodies can occur with any cIg-producing B-cell lymphoma. They are not limited to immunocytomas.

Cell Nucleus

[The staging diagnosis of Hodgkin's disease. A comparison of laparotomy and noninvasive methods].

The diagnostic efficiency of modern noninvasive methods more and more puts into question the need for exploratory laparotomy to determine the stage of Hodgkin's disease. In 208 patients (122 men and 86 women; mean age 29 [14-62] years) pre- and postoperative findings as to stage of the abdominal disease were compared. All patients had first been examined by ultrasound and computed tomography, followed by laparotomy with splenectomy. Findings of lymphography were available for 171 patients. Gross and microscopic examination of the tissues obtained by splenectomy and lymphadenectomy, as well as liver biopsy provided different stages from the preoperative ones, which in 46 had been false-negative, and in 16 false-positive. Spleen weight and involvement of the spleen with Hodgkin infiltration correlated only weakly with one another. In 38 of 41 patients with parapancreatic and splenohilar lymphnode involvement the spleen was also affected. These results indicate that regarding the stage of Hodgkin's disease, noninvasive methods so far do not achieve the validity of pathological examination obtained at exploratory laparotomy with splenectomy.

Adolescent

Nuclear grading of renal cell carcinomas--is morphometry necessary?

Comparative investigations of subjective with objective nuclear grading methods of renal cell carcinomas are almost completely lacking. Therefore, we graded 94 cases of this carcinomas by a simple, subjective microscopical estimation as well as by a morphogenetic measurement of nuclear area. Both procedures proved prognostically useful, but the best results were achieved by morphometry. By this method three prognostic groups of renal cell carcinoma were found, provided that the borderlines were drawn at 28 microns 2 and 60 microns 2, respectively. Particularly favourable and unfavourable cases could be separated from average ones, if the means and standard deviations of both the nuclear areas and the diameters were evaluated. Overall, morphometric nuclear analyses are highly desirable, if, for example, morphological data are to be used in the context of prognostic or therapeutic studies on renal cell carcinoma. However, there is a broad distribution of the values for individual cases so that, tumour-biologically, no exact demarcation of prognostically different groups can be expected.

Adult

[Deep mycoses in leukemia and malignant lymphoma].

1053 autopsies were performed from 1976 to 1990 in patients with leukemia and malignant lymphomas. At autopsy 184 of these (17.4%) presented with deep seated mycoses. There was an increasing percentage of mycoses per year with a maximum of 30% in 1990. Today deep seated mycoses are the most frequent letal complication in hematologic neoplasias. As expected their number was especially high in patients with acute leukemia but in recent years they were nearly just as numerous in myeloproliferative disorders. Among NHL they were twice as frequent in low grade cases as in high grade cases possibly due to a different extent of bone marrow infiltration. In contrast to former years more aspergilloses than candida infections are found, probably as a result of antimycotic therapy.

Acute Disease

[Autopsy results of deep mycoses in hematologic neoplasms (1053 patients].

1053 autopsies were performed during the period from 1976 to 1990 in patients with leukaemia and malignant lymphomas. At autopsy 184 of these (17.4%) presented with deep-seated mycoses. There was an increasing percentage of mycoses per year with a maximum of 30% in 1990. Today deep-seated mycoses are the most frequent lethal complication in haematologic neoplasias. As expected their number was especially high in patients with acute leukaemia but in recent years they were nearly just as frequent in myeloproliferative disorders. Among Non-Hodgkin lymphomas (NHL) they were twice as frequent in low-grade cases as in high-grade cases possibly due to a different extent of bone marrow infiltration. In contrast to former years more aspergillosis than Candida infections are found, probably as a result of antimycotic therapy.

Autopsy

Acute megakaryoblastic leukemia: a case report.

We present a case of acute megakaryoblastic leukemia identified by electron microscopy and platelet-specific antibodies. The histological examination of bone marrow showed distinct myelofibrosis. In accordance with recent communications, low-dose cytosine arabinoside treatment (20 mg twice daily s.c. over 21 days) was initiated. The subsequent bone marrow examination showed a severe hypoplasia with persistent blasts. Amsacrine and VP-16 were given without success. Finally the patient died of septicemia without proof of pathogen uninfluenced by antibiotic and antiseptic therapy 6 weeks after diagnosis. Our case report confirms the poor prognosis of acute megakaryoblastic leukemia.

Acid Phosphatase

[Initial symptoms of malignant thyroid tumors: the effect of age and sex in an iodine-deficient region. Experiences with 1116 patients].

Initial symptoms of thyroid cancer were collected and analysed for 1116 patients with thyroid cancer in an iodine-deficient region, retrospectively for the period 1960-80 (604 patients), prospectively for 1981-87 (512). Using the WHO classification, 56.1% of patients had papillary, 32.7% follicular, 4.8% C-cell, 3.7% anaplastic and 2.7% various other malignant tumours. In 40% of all patients the initial sign had been a solitary intrathyroid nodule. Cervical lymph node swelling as initial sign had been significantly more frequent in men (21.1%) than in women (10.3%; P less than 0.003). In patients aged under 40 years the cervical lymph node signs were three times as common as among those over 50 years. Distant metastases as initial sign of papillary carcinoma were seen only in those over 60 years. Tumour stages T3 and T4 were seen significantly more frequently in over 60-year-old (42.2%) than under 40-year-old (25.1%; P less than 0.001), independent of histological type. Composition and initial signs of this patient cohort in an iodine-deficient region differed only slightly from those in an iodine-rich region.

Age Factors

[Ultrastructural findings in tissue mast cells in urticaria pigmentosa].

In a study on 10 patients suffering from urticaria pigmentosa, biopsies of skin lesions were electron microscopically investigated. In contrast to normal skin, the mast cells showed irregular, partly bilobed nuclei, prominent nucleoli, hypogranulation, and rather small granules; giant granules were rarely observed. In addition, we frequently found degranulation, and the development of microvilli was much more prominent than with normal mast cells. These deviations from normal skin represent at least in part functional alterations. However, some of the findings suggest that urticaria pigmentosa may be considered a neoplastic disease of the tissue mast cells, although clear evidence is still lacking. In any case, our findings show that mast cells in mastocytosis are not identical with those in normal skin.

Biopsy