Pulmonary lymphangioleiomyomatosis: quantitative analysis of lesions producing airflow limitation

The lungs of three patients dying of lymphangioleiomyomatosis (LAM), which in two of the patients was associated with tuberous sclerosis, were studied to characterize better the sites of airflow limitation in this condition. Quantitative studies showed that small airways were narrowed and collapsed because of the surrounding emphysema, but few airways contained excess smooth muscle. These findings suggest that the airspace lesions are more important than muscular proliferation in small airways in producing airflow limitation. In the two patients who had LAM with tuberous sclerosis, sex steroid assays were negative. Pleurodesis controlled pleural effusions in all three patients but may have contributed to reductions in lung volume.     

The immunoarchitecture of cutaneous pseudolymphoma

The immunoarchitecture of five cutaneous pseudolymphomas was studied by staining serial sections for T- and B-cell and dendritic reticulum cell (DRC) antigens with monoclonal antibodies, and compared with that of reactive lymph nodes and cutaneous lymphoma. In four cases compartmentalization of B and T cells was observed, analogous to findings in reactive lymph nodes. In two of these cases the immunoarchitectural features were strikingly similar to those of reactive lymph nodes. Both had distinct follicles with germinal centers, and in one distinct mantle zone formation was seen. B cells in the follicles were polyclonal, with kappa chain predominance. The germinal centers showed the expected intercellular and/or dendritic pattern of immunoglobulin heavy chain, B2, and DRC-antigen expression. T cells admixed in the germinal centers were overwhelmingly of the T-helper type. The B-cell compartments in the other two cases showed some subtle immunologic evidence of aberrance, but the weight of evidence suggested reactive/aberrant rather than malignant processes. The T-cell compartments in all four cases showed a predominance of T-helper and a minority of T-suppressor/cytotoxic cells. All contrasted with the lymphomas, which showed B-cell monoclonality, markedly deranged T-subset proportions, or novel T-cell phenotypes. Although the main focus of this study was cases involving substantial populations of both B and T cells, preliminary observations were made in one case in which a predominance of T cells and prominent epidermotropism simulated mycosis fungoides. Quantitative ultrastructural analysis in this case suggested a reactive T-cell process. Leu-6-positive Langerhans cells were increased in the epidermis and dermis in all five cases, and in the dermis they were found almost exclusively in T-cell compartments. It is proposed that this distribution is the anatomic correlate to the known functional role of Langerhans cells in antigen processing/presentation and T-cell activation. In the cutaneous "lymph node equivalent," Langerhans cells are analogous to interdigitating reticulum cells of reactive lymph nodes in distribution and, probably, in function. The DRC found in the germinal centers in two cases were probably antigenically identical and functionally analogous to those in germinal centers of reactive lymph nodes. Immunologic phenotyping of serial cutaneous sections may aid in distinguishing reactive from neoplastic lymphoid lesions. Immunoarchitectural analysis promises to be a powerful tool for the study of lymphoproliferative disease.     

Fluorescence of damaged myocardium in endomyocardial biopsy specimens for the evaluation of cardiac transplantation

Sections stained with hematoxylin-eosin from 138 endomyocardial biopsy specimens were examined in a Zeiss epifluorescent ultraviolet microscope for fluorescence indicative of myocardial injury. The biopsy specimens had been obtained from cardiac transplant recipients for routine follow-up evaluation or due to clinically suspected episodes of rejection. Yellow fluorescence and/or granularity of necrotic myofibers (with normal myocardium appearing olive green to yellow-brown), as reported in autopsy series, was observed in 22 of our specimens, for which the results of staining with hematoxylin-eosin and/or trichrome were found to contain areas of fiber fluorescence that were not recognized by staining with hematoxylin-eosin or trichrome. In some areas in an additional 13 specimens, the fiber damage seen on ultraviolet examination was greater than that suspected on the basis of the light microscopic morphologic changes. In seven cases routine light microscopy revealed fiber necrosis that could not be confirmed by ultraviolet illumination study. Fluorescence of damaged myofibers under ultraviolet illumination may contribute to the detection of early or mild myocardial injury in endomyocardial biopsy specimens from cardiac transplant recipients.     

Potential applications of a human tumor stem cell bioassay to the cytogenetic assessment of human cancer

Our group recently developed a soft agar colony bioassay for the study of human tumor stem cells. Initial applications of this bioassay to the cytogenetic assessment of a variety of human solid tumors has been very promising. The advantages inherent to cytogenetic sampling of the clonogenic tumor cells within colonies reside in the marked quantitative and qualitative enhancement of metaphase chromosomes. Due to the large number of potentially analyzable mitotic figures in many tumor clusters following as little as 24–48 hr in culture, utilization of standard Giemsa, G-, C-, and NOR-banding techniques has been possible. We feel this technique will overcome a variety of the technical difficulties inherent to the cytogenetic study of both human solid tumors and hematopoietic malignancies.     

Distinguishing characteristics of a new neuroblastoma cell line

The characteristics of a new neuroblastoma cell line (MC-NB-1) established from the bone marrow of a 2-year-old male are described. Morphologically, the cells appear as flattened and epithelial-like or as small and spherical. Electron microscopy demonstrated microtubules and dense core secretory granules. The doubling time was approximately 35 hr. Isoenzyme patterns and catecholamine secretion indicated a human line of neuronal origin. The soft agar tumor colony forming system demonstrated drug resistance in vitro comparable to in vivo nonresponsiveness. The stemline karyotype of MC-NB-1 is 44,Y,del(1) (p22:), -4, -7, +del(7)(q22:), -16, +t(7;16)(16pter leads to 16q24::7q22 leads to 7q32), -17. Additionally, double-minute bodies were observed. However, no evidence of homogeneous staining regions (HSRs) were detected.     

Karyotypic analysis of human ovarian carcinoma cells cloned in short term agar culture

We report detailed chromosome banding analysis of six cases of ovarian adenocarcinoma cultured 24–96 hr in a recently developed bioassay for clonogenic tumor cells. The results of G and C banding revealed a variety of chromosome changes including the observation of a simple deletion for a portion of the long arm of chromosome #6, del(6) (pter → q15–21:), in tumor cells from four of six patients. Our study indicates that short-term agar culture can provide a valuable tool in the study of tumor cell karyology. A comparison of our results with previously published studies suggests that in addition to alterations of chromosome #1, the deletion of 6q may represent a characteristic chromosomal aberration in ovarian carcinoma.     

Hepatic parenchymal lymphoid aggregates in Hodgkin's disease

One hundred twenty-three liver biopsies performed at staging laparotomy for Hodgkin's disease were reviewed. Discrete parenchymal lymphoid infiltrates with variable cytologic atypia were identified in 12 patients. None of these patients had liver involvement by Hodgkin's disease. All 12 patients were alive with no clinical evidence of liver disease at last follow-up examination; however, two had extrahepatic relapses of Hodgkin's disease. Parenchymal lymphoid aggregates, a nonspecific finding in the livers of patients with Hodgkin's disease, may show some degree of cytologic atypia, but they do not represent lymphoma. Such aggregates may be relatively common and they may be overinterpreted as neoplastic, particularly in patients with non-Hodgkin's lymphoma.     

An immunohistologic study of the epithelial and lymphoid components of six thymomas

Six thymomas were classified histologically and studied immunohistochemically with a panel of mouse and rat monoclonal antibodies directed against thymic epithelial and lymphoid components. The antibodies included monoclonal antibodies directed against cytokeratin, medullary epithelial cells (ER-TR5), and HLA-DR and HLA-ABC antigens, as well as antibodies with specificity for thymocytes. Histologically, one thymoma was characterized by epithelial predominance (EP type), two showed lymphoid predominance (LP type), and two showed mixed lymphoid/epithelial composition (MLE type); one thymoma was a malignant pure epithelial thymoma (PE type). In the thymomas of the MLE and EP types the major populations of cells consisted of HLA-DR-negative, cytokeratin-positive epithelial cells with large ER-TR5-positive subpopulations (i.e., the phenotype of medullary epithelium). In the thymomas of the LP type, the neoplastic population was composed of cytokeratin-positive, ER-TR5-negative cells that expressed the HLA-DR antigen (i.e., the phenotype of cortical epithelium). The thymoma of the PE type consisted of cytokeratin-positive cells, some of which were ER-TR5- and HLA-DR-positive. Double immunofluorescence studies revealed the presence of varying numbers of additional nonepithelial (nonlymphoid) HLA-DR-positive cells in thymomas of the LP, MLE, and EP types. The intervening lymphoid population in the thymomas of the LP, MLE, and EP types consisted largely of cortical thymocytes, as defined by immunologic characterization. These results suggest that thymomas can be classified as medullary or cortical epithelial neoplasms on the basis of their immunologic phenotypes.     

Subclassification of small cell cancer of the lung: the Southeastern Cancer Study Group experience

Cancers in more than 300 patients being treated by Southeastern Cancer Study Group protocols for small cell carcinoma of the lung (SCCL) were subclassified as oat cell or intermediate types by criteria developed by two groups of investigators. With Cox survival and logistic regression models, no differences in survival or responsiveness to therapy were found between these types of tumors. These and previously published results suggest that the only intermediate tumors worth distinguishing are the "22/40" tumors with morphologic features precisely intermediate between those of SCCL and non-SCCL, including mildly vesicular nuclei, common small nucleoli, and rims of stained cytoplasm. Such tumors are the dividing point between SCCL and non-SCCL and constitute a small fraction of the spectrum from SCCL to non-SCCL.     

Primary malignant melanomas of the lung and adrenal

Malignant melanoma originating outside the skin, juxtacutaneous mucous membranes, eyes, and leptomeninges is a very rare neoplasm. Two such primary visceral malignant melanomas from the lung and adrenal are described in detail.     

Laboratory assessment of nutritional status

Malnutrition is one of the major causes of increased morbidity and mortality among hospitalized patients. The availability of nutritional therapy for these patients has made clinicians aware of the need for reliable methods of nutritional assessment. A variety of anthropometric, biochemical, and immunologic parameters has been used as indicators of protein-calorie malnutrition. Recently, the concentration of several rapid-turnover visceral proteins (transferrin, thyroxine-binding prealbumin and retinol-binding protein) has been shown to be a very sensitive parameter for indicating both the efficiency of nutritional therapy and conditions of borderline protein intake in apparently healthy children. Likewise, several immunologic parameters (including T cells, delayed hypersensitivity response, and complement components) have been shown to correlate with morbidity, mortality risk, sepsis, and death.     

B-cell neoplasms of the lymphocytic, lymphoplasmacytoid, and plasma cell types: immunohistologic analysis and clinical correlation

The relation between chronic lymphocytic leukemia (CLL, lymphocytic lymphoma (SL), plasmacytoid lymphocytic lymphoma (LP), plasmacytoma (PL), and multiple myeloma (MM) was investigated with cryostat sections stained with antibodies to immunoglobulin heavy and light chains and the B-cell differentiation antigens B1, B2, Ia, T1, and CALLA. Neoplasms were subclassified according to plasmacytoid features, leukemia (CLL) site of involvement (nodal or extranodal), serum monoclonal immunoglobulin, or clinical evidence of MM. The results defined two groups of lymphocytic lymphomas without plasmacytoid features (16 cases). Ten of these lymphomas were associated with CLL. Nine involved lymph nodes, all expressed IgM, five expressed IgD, nine were B2-positive, eight were T1-positive, and all were B1- and Ia-positive. Six of the lymphomas were not associated with CLL. Five of these tumors were extranodal, all were T1- B1+ B2- Ia+, five expressed IgM without IgD, and one contained IgG. These differences in clinical and immunologic phenotypes suggest that CLL and SL without CLL may be related to different stages of B-cell differentiation. T1 appeared to be a marker for CLL, since all T1-positive neoplasms were leukemic. Lymphomas with plasmacytoid features (ten cases) were more often extranodal, and none was leukemic. The immunologic phenotypes were heterogeneous: all of these lymphomas were T1-negative, most were IgM+ IgD-, three were B2-positive, and all were Ia-positive. The plasma cells in five lymphomas with marked plasmacytoid features were B1-negative; they were Ia-positive in four and Ia-negative in one. These data suggest that LP is a heterogeneous group, reflecting B cells at diverse stages of differentiation. Ten plasmacytomas, nine of which were associated with MM, differed from LP in showing heavy chain class switching; all were T1- B1- B2-, and all but one were Ia-negative. These results are consistent with the existence of two pathways or stages of B-cell differentiation: one that generates IgM-producing plasma cells, as seen in the primary immune response or in response to pokeweed mitogen, and one that generates IgG- or IgA-positive plasma cells, as seen in the late primary or secondary immune response. Plasmacytoid lymphocytic lymphoma reflects the first, while PL/MM reflects the second pathway. B1 appears to be lost before Ia in terminal plasma cell differentiation.     

Bone marrow changes in patients with hairy cell leukemia treated by recombinant alpha2-interferon

Bone marrow specimens from 21 patients with hairy cell leukemia (HCL) who were entered into a program to study the efficacy of treatment with recombinant alpha 2-interferon were evaluated. Patients were treated with the interferon, 2 X 10(6) U/m2 subcutaneously three times weekly, and were scheduled to undergo bone marrow aspiration and biopsy at study entry and after three (21 patients) and six (16 patients) months of treatment. Bone marrow samples after three months of treatment showed an overall decline in cellularity, from an average of 77 +/- 20 to 57 +/- 22 per cent, with a marked decrease in the percentage of neoplastic mass (from 87 +/- 9 to 59 +/- 24 per cent). The bone marrow changes were associated with significant improvement in hematologic values, including hemoglobin levels and granulocyte and platelet counts. The bone marrow changes and improved hematologic values remained stable with continuation of interferon therapy. However complete bone marrow remission did not occur in any of the patients after three or six months of interferon therapy. The HCL cell mass in more than 60 per cent of the patients remained at or above 50 per cent of the marrow cellularity and dropped to less than 25 per cent in 14 per cent of the patients. In all of the patients increased amounts of reticulin fibers were identified in the bone marrow prior to therapy, and 89 per cent of bone marrow aspirations failed (dry tap). The amounts of reticulin fibers remained increased in most of the patients (91 per cent), with a high incidence of dry taps (73 per cent), after therapy. Interferon therapy also changed the tartrate-resistant acid phosphatase(TRAP)-positive HCL cells to TRAP-negative, suggesting inhibition of activity and/or production of TRAP in HCL cells.     

Incidence of IgA-related nephritides in American Indians in New Mexico

The racial distribution of the findings in 664 renal biopsies was studied for the state of New Mexico. The incidence of IgA-related nephritides (Berger's disease and Henoch-Sch?nlein purpura) was significantly greater in American Indians than in Hispanics and Anglos; IgA-related nephritides were found in 38 per cent of renal biopsies in American Indians. The clinicopathologic presentations of IgA-related nephritides were similar in the three ethnic groups.