Christian Fellbaum

Castleman's disease. Differences in follicular dendritic network in the hyaline vascular and plasma cell variants

Twenty‐seven cases of the hyaline vascular variant and 10 cases of the plasma cell variant of Castlemans disease were studied with the paraffin resistant monoclonal antibodies Ki‐FDC1p and/or Ki‐M4p against follicular dendritic cells. Studies with the monoclonal antibody Ki‐M9, for the detection of sinus lining cells, were also performed on the available frozen tissue in four cases of the hyaline vascular variant. In nine of the 10 plasma cell variant cases, the predominant type of follicular dendritic cell network was similar to that seen in normal or reactive germinal centres. In contrast, the hyaline vascular variant demonstrated either an expanded, disrupted, follicular dendritic cell network (10 cases) or multiple tight collections of follicular dendritic cells (16 cases). Sinus lining cells were not detected in the four cases studied. The difference in the predominant type of dendritic meshwork is an additional distinguishing feature to separate the plasma cell and hyaline vascular variants of Castlemans disease. The patterns of dendritic network seen in the hyaline vascular type, together with the absence of sinus lining cells, appear to favour the hamartoma theory proposed for this variant.

Prognostic importance of histomorphologic subclassification for epithelial thymic tumors

AbstractBackground: The prognostic importance of various clinical variables (age, sex, association with myasthenia gravis), staging according to Masaoka, histologic type according to the Marino/Kirchner/Müller-Hermelink (MKM-H) classification, and residual tumor category (R category) was evaluated in a retrospective analysis. Methods: Eighty-two patients with epithelial thymic tumors (ETTs) treated in the period 1969–1993 were evaluated, and archived specimens were histologically reclassified according to the classification of MKM-H. Results: Age, sex, and association with myasthenia gravis were of no prognostic importance. The R category is of significant prognostic importance, with 5- and 10-year survival rates of 93.6% and 87.3%, respectively, for R0 resections compared with 0% at 5 years for R1 and R2 resections (p<0.001). Staging (Masaoka) proved to be a prognostic factor (5-/10-year survival: stage I, 100%/90.9%; II, 95%/88.2%; III, 55.9%/46.6%; and IV, 10.8%/10.8%; p<0.001). Histologic typing according to MKM-H is also of significant prognostic importance (5/10 year survival: thymomas: medullary, 100%/100%; mixed, 100%/100%, predominantly cortical, 68.6%/68.6%; cortical, 65.8%/65.8%; thymic carcinomas: well-differentiated type, 62.3%/44.5%; thymic carcinomas other than well-differentiated type, 33.6%/26.9%; p<0.001). Multivariate analysis demonstrated that staging (p<0.001), R category (p<0.026), and MKM-H classification (p<0.028) have an independent impact on survival. Conclusions: Staging (Masaoka), R category, and histologic classification (MKM-H) are important independent prognostic factors for patients with epithelial thymic tumors. Complete (R0) surgical resections should be the ultimate goal in the clinical management of patients with epithelial thymic tumors.

Pulmonary nodule caused by an alveolar adenoma of the lung

Alveolar adenomas of the lung may be a rare cause of solitary coin lesions on chest radiographs. We report a case of this neoplasm, describe its morphological and immunohistochemical characteristics and give further evidence that alveolar adenomas of the lung represent a benign proliferation of both the alveolar epithelium and the septal mesenchyme.

Follicular dendritic cells in extranodal non-Hodgkin lymphomas of MALT and non-MALT type

Extranodal lymphomas of the thyroid (n=19), kidney (n=15) and testis (n=30) were investigated histologically and immunohistochemically for follicular dendritic cell pattern using the monoclonal antibody Ki-FDC1P. This recognizes follicular dendritic cells in paraffin sections. Follicular dendritic cells were most predominant in lymphomas of the thyroid. These thyroid lymphomas showed the morphological features of mucosa-associated lymphoid tissue (MALT) type lymphomas in 18 of 19 cases and were classified as high-grade malignant lymphoma of MALT type with evidence of a low-grade malignant component (n=18). Ten of these cases contained destroyed reactive follicles of follicular dendritic cells. In 6 of these 10 cases follicular dendritic cells occurred in a pattern of tumour-associated abortive follicle type. The remaining lymphoma of the thyroid was an immunoblastic lymphoma of B-cell type showing no detectable follicular dendritic cells. In extranodal lymphomas of non-MALT type follicular dendritic cells occurred in only two cases where immunocytoma involved the kidney. Malignant lymphomas of the kidney (chronic lymphocytic leukaemia,n=2; immunocytoma,n=4; centroblastic lymphoma,n=9) and of the testis (immunocytoma,n=2; centroblastic lymphoma,n=27; immunoblastic lymphoma of B-cell type,n=1) revealed no characteristics of MALT type lymphoma, cytologically or with respect to follicular dendritic cells. Classical lymphoepithelial lesions formed by centrocyte-like cells, a hallmark of MALT, occurred exclusively in thyroid lymphomas of MALT type. Although occurrence of classical lymphoepithelial lesions formed by centrocyte-like cells was limited to thyroid lymphomas of MALT type, a growth pattern of lymphoid blasts, with formation of lesions mimicking lymphoepithelial lesions superficially, was found in 6 of 27 testicular centroblastic lymphomas. Follicular dendritic cells in non-Hodgkins lymphomas of MALT type show distinct follicular patterns not found in other extranodal lymphomas such as those found in the kidney and testis.

Large cell anaplastic lymphoma: Evaluation of immunophenotype on paraffin and frozen sections in comparison with ultrastructural features

Eleven cases of large cell anaplastic lymphoma (T typen=5, B typen=4, 0 typen=2) were investigated using electron microscopy and immunophenotyping on formalin-fixed paraffin sections and frozen sections of fresh tissue, to determine whether morphological criteria exist for the discrimination of T, B, and 0 phenotypes. Tumour cell lineage could not be established from ultrastructural features. On paraffin material monoclonal B-cell markers Ki-B5 and L-26 served as reliable tools for recognizing the B phenotype of large cell anaplastic lymphomas (previously determined on fresh material), whereas monoclonal antibodies MT1 (CD43) and UCHL1 (CD45RO) were of limited value in lineage determination.

c-myc mRNA expression in non-Hodgkin’s lymphomas

SummarySteady state c-myc mRNA levels determined by Northern blot analysis were examined in non-Hodgkin’s lymphomas (NHL) of both high (n = 29) and low malignancy (n = 18), and in non-specific chronic lymphadenitis (n = 6). High grade NHL, classified according to the updated Kiel classification, revealed significantly larger amounts of c-myc mRNA compared with low grade NHL and lymphadenitis. mRNA levels in nonspecific lymphadenitis were lower than in low grade NHL, but the differences were not statistically significant. No correlation between c-myc mRNA levels and the immunologic phenotype was discernible. Growth fractions of the NHL were determined by immunostaining with the monoclonal antibody Ki-67. Significant correlations between the percentages of Ki-67-positive cells, as well as the amounts of c-myc mRNA, and classification into high or low grade NHL were found. However, the percentage of Ki-67 positive cells and c-myc mRNA levels in individual cases and in the various histologic entities of NHL did not correlate. Our results indicate the overexpression of the c-myc gene in NHL, and a highly significant correlation of steady state c-myc mRNA levels with the prognosis-related histomorphologic Kiel classification of NHL into different subgroups of low and high grade malignancy.

Investigation of the comparative effects of 2-chlorodeoxyadenosine on tumor colony forming unitsin vitro

Summary2-CdA is a deaminase-resistant purine analogue which has shown clinical activity against various hematological tumors, and is currently undergoing clinical phase II trials. The objectives of our study were to determine the activity of 2-CdA against freshly explanted clonogenic cells from non-hematological human tumors and compare this agent with other clinically useful anticancer agents. We also compared short-term (1 hour) and long-term (21–28 days) exposures. For short-term exposure (1-hour), final concentrations were 0.57, 5.7, 57, and 114 ng/ml. Inhibition of tumor specimens was concentration-dependent: 0.57 ng/ml: 1/51 (2%), 5.7 ng/ml: 4/52 (7%), 57 ng/ml: 11/52 (21%), 114 ng/ml: 27/50 (54%). At concentrations ≥57 ng/ml, 2-CdA was as active as cisplatin, doxorubicin, 5-fluorouracil, mitomycin-C, vinblastine, and etoposide. For long-term exposure (21–28 days), final concentrations of 2-CdA were 0.57, 5.7, and 57 ng/ml. At 0.57 ng/ml, 2-CdA was active in 4/54 (7%) specimens [5.7 ng/ml: 13/54 (24%), 57 ng/ml: 40/54 (74%)]. A head-to-head comparison with short-term exposures demonstrated greater activity if the drug exposure time was extended. Using the strategy for testing other standard agents (in vitro dose of 1/10th achievable peak plasma concentration), one would predict clinical response rates for single agent bolus or short-term administration of 2-CdA to be in the neighborhood of 7%. Longer durations of infusion or multiple doses might increase the response rate to about 24%. If higher peak plasma concentrations could be achieved, dose-dependent increases in clinical responses might be achievable. We conclude that 2-CdA is active against clonogenic cells from freshly explanted non-hematological human tumor specimens at high concentrations.