Activation of Cl, the first component of complement, the generation of Clr-Cls and Cl- inactivator complexes in normal serum by heparin-affinity chromatography

Investigations facilitating heparin-affinity chromatography and immunochemical procedures were utilized to study the interaction and behaviour of heparin with C1, C1 subcomponents and C1&;#x0304; IA in normal serum.Clq bound to heparin-Sepharose independent of divalent cations at 4 and 37° C at physiological pH and salt concentration requiring a high salt concentration for its complete release. MacromolecularC1 bound to heparin-Sepharose in the presence of Ca²⁺ at 37°C, activating Clr and Cls in the process as demonstrated by the appearance of C1&;#x0304;r-C1&;#x0304;s-C1&;#x0304; IA complexes when purified C1&;#x0304; IA was added to the eluted fractions. At 4° C however, proenzyme C1r and C1s were present in the eluted fractions. Proenzyme C1r-C1s and C1&;#x0304;r-C1&;#x0304;s-C1&;#x0304; IA complexes did not bind directly to heparin-Sepharose. Binding of C1r-C1s in the presence of Ca²⁺ was dependent on Clq bound to heparin.High levels of proenzyme C1r-C1s complexes were produced during the 4°C experiments in the presence of Ca²⁺ and were collected in the void volume.C1&;#x0304;r-C1&;#x0304;s-C1&;#x0304; IA complexes generated during the 37°C experiments had no affinity for heparin-Sepharose. C1&;#x0304; IA did not bind directly to heparin. Recirculation of a serum sample collected after Clq was removed by heparinaffinity at 4°C in the presence of EDTA demonstrated that (1) Clr and Cls in the presence of calcium could be reassembled with heparin-bound Clq to form macromolecular Cl. (2) Clr and Cls in non-activated forms did not bind directly to heparin-Sepharose. (3) Clr and Cls contained in the reassembled Cl/heparin complex at 37°C were in active enzymic forms.     

Lipomatous tumors: a correlative cytologic and histologic study of 27 tumors examined by fine needle aspiration cytology

A correlative cytologic and histologic study of 12 benign lipomatous tumors and 15 liposarcomas (well-differentiated, myxoid, round cell, and pleomorphic) is presented. In two cases the fine needle aspiration material was embedded in Epon for light and electron microscopic examination. Good correlation was found between the histologic and cytologic findings in the fine needle aspiration material. Pitfalls in the cytologic diagnosis of regressively changed lipoma, intramuscular lipoma, angiolipoma, hibernoma, and lipoblastoma, which may lead to an erroneous diagnosis of liposarcoma, are illustrated. The cytologic appearances of the liposarcomas varied with histologic type, although in all of these tumors the main criterion was the presence of atypical multivacuolated lipoblasts with characteristically scalloped nuclei. Staining of the aspirated material with Alcian blue at varying pH levels for characterization of the glycosaminoglycan content may help in the distinction of myxoid liposarcomas from myxoid chondromatous tumors and chordomas. May-Grünewald-Giemsa staining is considered the most useful staining method, while fat staining is considered of limited or no value in the cytologic diagnosis of lipomatous tumors. Epon embedding of fine needle aspirates for light and electron microscopic examination seems to be a useful diagnostic technique.     

A distinctive glomerular lesion complicating placental site trophoblastic tumor: report of two cases

Renal disease with distinctive pathologic features developed in two young women who had placental site trophoblastic tumors. The renal abnormalities were manifested by proteinuria in both cases and by hematuria in one case; blood pressure was elevated in one of the patients. Pathologic examination of the kidneys showed distinctive glomerular abnormalities, characterized mainly by the presence of occlusive eosinophilic deposits in many of the glomerular capillary lumina, most of which stained for fibrinogen-related antigens and IgM by immunohistochemical techniques. Ultrastructural examination showed the deposits to consist mainly of granular material that contained packets of fibrillar material with the appearance of fibrin. The uterine tumors were composed of mononucleated and multinucleated cells with abundant cytoplasm that infiltrated between the muscle bundles of the myometrium; in both tumors there was prominent deposition of eosinophilic material that had the tinctorial properties of fibrin and that stained for fibrinogen and IgM in immunoperoxidase studies. The renal abnormalities disappeared after hysterectomy in one case; the other patient, who was receiving chemotherapy and had disseminated intravascular coagulation, died with leukopenia and sepsis. The clinical and pathologic features in these cases suggest that the renal abnormalities were related to the uterine tumors and that the production of immune complexes and/or the activation of intravascular coagulation by the tumors were pathogenetic mechanisms.     

Cytogenetic analysis of 62 transitional cell bladder carcinomas

Chromosome analysis of biopsy material obtained after vinblastine pretreatment was carried out in 108 specimens from 89 patients with transitional cell carcinoma of the urinary bladder. Analyzable metaphases were obtained in 62 tumors, but only in nine tumors could karyotypes be analyzed by banding; a conventional technique was used in all others. Ploidy and occurrence of markers corresponded with tumor morphology and invasion and sometimes aided in the clinical evaluation; chromosome anomalies specific for bladder cancer were not revealed. In noninvasive tumors of WHO grade 1 and 2, near-diploid karyotypes with occasional marker chromosomes dominated. Grade 3 tumors showed a variety of grossly aneuploid karyotypes, with an almost constant occurrence of different markers. Superficially invasive G2 tumors had moderately pronounced aberrations with more deviations than noninvasive tumors but without the great variety of G3 tumors.     

Micronuclei in erythropoietic bone marrow cells: Relation to cytogenetic pattern and prognosis in acute nonlymphocytic leukemia

The bone marrow karyotype and the frequency of micronuclei in erythropoietic bone marrow cells (Howell-Jolly bodies) were determined in 25 adults with acute nonlymophocytic leukemia (ANLL). Ten patients had exclusively normal diploid bone marrow cells; 11 had a mixture of normal and abnormal cells, and 4 had abnormal bone marrow metaphases only. The frequency of micronuclei ranged from 3 to 28/2000 erythropoietic bone marrow cells (median 10). The number of micronuclei was significantly higher in patients with abnormal metaphases than in those with normal metaphases; in patients with a mixture of normal and abnormal bone marrow metaphases there was an association between the frequency of abnormal metaphases and the number of micronuclei. A striking difference in median survival time was found between patients with low and high numbers of micronuclei, irrespective of the cytogenetic bone marrow patterns. Patients with fewer than 10 micronuclei per 2000 erythropoietic bone marrow cells had a median survival of 148 days; those with more than 10/2000 had a median survival of only 34 days (0.002 < p < 0.02).     

Sebaceous glands within the thymus: report of three cases

Sebaceous glands in the thymus were discovered in three patients--two with myasthenia gravis and the other, who was operated on because of aortic valvular disease--with an unsuspected thymoma. Sebaceous glands not associated with hair follicles occur in diverse sites, the majority of which are in the head and neck or anogenital regions. Although most of these sites arise from the ectoderm, sebaceous glands have been reported in a thyroglossal duct, the larynx, and the esophagus, which are entodermal structures. Thus, precedents for ectodermally derived sebaceous glands in endodermal sites exist, but sebaceous glands have not previously been reported in the thymus. The authors speculate that their occurrence in the thymus may be related to the reported ectodermal contribution to the developing thymus by the epibranchial placode or cervical sinus.     

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.     

Keratin proteins and carcinoembryonic antigen in synovial sarcomas: an immunohistochemical study of 24 cases

Twenty-four synovial sarcomas were examined for the presence of keratin proteins by an indirect immunoperoxidase method with paraffin-embedded tissues. Keratin proteins were identified in 16 of 24 cases (67 per cent). Both the pseudoglandular and spindle cell areas of all eight of the biphasic synovial sarcomas and the spindle cells of eight of the 16 monophasic synovial sarcomas contained keratin proteins. In spindle cell areas, staining was observed in single cells and small cords and clusters of cells in the absence of cleft formation or other evidence of a pseudoglandular component. The predominant cytologic staining pattern in all cases was peripheral, with localization of staining to the cell membrane or adjacent areas, but diffuse and focal cytoplasmic staining patterns were also observed. No staining for keratin proteins was seen in 101 control cases, including 52 sarcomas of various types. Carcinoembryonic antigen was also identified in four of the 24 synovial sarcomas by an indirect immunoperoxidase technique. The identification of keratin proteins may be helpful in the pathologic diagnosis of synovial sarcoma, particularly the spindle cell monophasic variant.     

Primary malignant lymphoma of the lung: histopathologic and immunologic evaluation of nine cases

Nine primary malignant lymphomas of the lung are described. Seven were localized lesions, and two were diffuse bilateral infiltrations. Histopathologic examination of these lesions suggests that they represent examples of the same entity and that it is a malignant lymphoma rather than a reactive infiltration or "pseudolymphoma." Histologic evidence of lymph node involvement is unusual, even in the presence of mediastinal or pleural infiltration. Immunohistochemical studies demonstrated a monotypic B-cell population in cases in which suitable tumor tissue was available for study (four of nine). Of the other five cases, two had a population of monotypic B lymphocytes in the peripheral blood, and in one of these and in one additional case gastric lymphomas subsequently developed. It is suggested that these lymphomas arise from bronchus-associated lymphoid tissue, which would explain both their histologic features and their tendency to remain localized to the lung for long periods.     

Chromosomes in neoplasia: An appeal for unpublished data

In relation to a recent survey of chromosome aberrations in 856 human neoplasms the following points are presented: 1) the chromosome aberrations of significance to the biology of neoplasms are nonrandom; 2) aberrations of a particular chromosome tend to be of similar kind; 3) aberrations cluster to a limited number of specific chromosomes; 4) geographic differences have been observed in chromosome aberrations; 5) the karyotypic pattern of a neoplasm may be influenced by previous exposure to potential carcinogenic agents; 6) the role of chromosome aberrations in neoplasia—a hypothesis; 7) a plea is made for unpublished data to be included in our next survey of chromosome aberrations.     

Squamous cell carcinoma of the breast: a clinicopathologic analysis of eight cases and review of the literature

Malignant neoplasms of the female breast composed of squamous cells are rare and constitute a particularly poorly understood facet of breast disease. Two pure squamous cell carcinomas ( SCCs ) of the breast and six tumors that displayed various combinations of malignant squamous elements and ductal breast adenocarcinoma were identified. Electron microscopy confirmed the diagnosis of SCC in two cases by the demonstration of regularly spaced desmosomes, tonofilament bundles, and keratohyaline granules. A review of the literature indicated that breast cancers with components of SCC are histologically variable. Approximately 30 cases of pure SCC and 80 cases of mixed adenocarcinoma and SCC (adeno-SCC) have been reported. Some of these squamous epithelium-containing tumors have displayed areas of cyst formation, spindle cell metaplasia, and pseudosarcomatous desmoplastic response, or origins in preexisting breast lesions, such as cystosarcoma phyllodes or dermoid cysts. Although this variability indicates a heterogeneous group of neoplasms, the overall prognosis for carcinomas of the breast with malignant squamous elements appears to be quite similar to that for ordinary breast adenocarcinomas of similar size and stage.     

Pathologic pulmonary findings in children with the acquired immunodeficiency syndrome: a study of ten cases

Lung tissue and tissue from the lymphoreticular system obtained at open biopsy and/or autopsy were studied in ten children with the acquired immunodeficiency syndrome (AIDS). One or both parents of nine of the children had AIDS or risk factors for AIDS. The remaining child had hemophilia. The following pulmonary lesions were seen: 1) diffuse alveolar damage (DAD), 2) Pneumocystis carinii and/or cytomegalovirus pneumonitis, 3) lymphoid interstitial pneumonitis (LIP), and 4) desquamative interstitial pneumonitis (DIP). Combinations of such factors as mechanical ventilation, oxygen therapy, and opportunistic infection played a role in the pathogenesis of DAD. Opportunistic infections were related to the defective cell-mediated immunity in these children. The clinical, epidemiologic, immunologic, and pathologic features of the thymuses of these patients indicate that the immune deficiency was unlikely to have been of congenital origin. The immunologic abnormalities may also have been related to the pathogenesis of LIP and DIP. Neither LIP nor DIP has been described in adults with AIDS. Open lung biopsy is of practical importance in the diagnosis and treatment of pulmonary disease in children with AIDS.     

Silicone granulomas: report of three cases and review of the literature

Since silicone is rapidly becoming one of the most commonly used biomaterials in modern medicine, pathologists will be observing increasing numbers of cases of silicone-related disease. Although numerous case reports have established that silicone elicits a characteristic response in tissues, the varying tissue reactions to silicone gels, liquids, and elastomers (rubber) have not been emphasized. Three cases are reported, and the literature is reviewed to illustrate the varying features of tissue reaction to silicone in its different forms. The first case is an example of silicone lymphadenopathy in an inguinal lymph node. This case demonstrates exuberant foreign body granuloma formation in response to particles of silicone elastomer. The second case involves a patient who had facial subcutaneous liquid silicone injections, and the third case is that of a woman in whom breast carcinoma developed 13 years after mammary augmentation with liquid silicone injections. These two cases illustrate the characteristic reaction to silicone liquid, with numerous cystic spaces and vacuoles in the soft tissues but minimal or no foreign body giant cell reaction. Scanning electron microscopy and energy dispersive x-ray analysis were performed in the first two cases, confirming the presence of silicon. Silicone migration and the clinical significance of various silicone-induced lesions are discussed.     

Anatomic analysis of removed prosthetic heart valves: causes of failure of 33 mechanical valves and 58 bioprostheses, 1980 to 1983

The details of heart valve prosthesis-associated problems are not widely known. This study investigated the etiologies of the failures of 91 valves, 33 mechanical prostheses and 58 bioprostheses, obtained at reoperation (83) or autopsy (eight) at the Brigham and Women's Hospital during the 42-month period from mid- 1980 through 1983, one to 264 months (mean, 72 months) after valve replacement. Analysis was by gross, histologic, radiographic, and microbiologic examination, as well as review of clinical records. Overall causes of failure included paravalvular leak (15 per cent), thrombosis (7 per cent), tissue overgrowth (8 per cent), degeneration or mechanical failure (43 per cent), and endocarditis (19 per cent). Endocarditis and paravalvular leak were equally frequent with mechanical prostheses and bioprostheses. In addition, thrombosis (18 per cent), tissue overgrowth (21 per cent), and structural failure (12 per cent) were all important failure modes for mechanical prostheses. Sterile degeneration was the overwhelming cause of failure for bioprostheses, accounting for the failure of 35 of 58 (60 per cent) of those recovered. Sterile degeneration took several forms: calcification, with or without cuspal tears (27 cases, 47 per cent of bioprostheses; mean, 77 months, range, 44 to 108 months) and cuspal defects without calcification (eight cases, 14 per cent; mean, 59 months, range, eight to 122 months). In general, calcification increased with time after implantation, but the propensity for the mineralization of bioprostheses varied widely among patients. Four torn valves that had been in place for more than six years had radiographically undetectable calcific deposits. The results of this study indicate that paravalvular leak and endocarditis are frequent causes of failure for all valve types. No clear failure mode predominates with mechanical valve prostheses, although some designs have specific inherent limitations. In contrast, degeneration, especially that related to mineralization, is the most important cause of the late failure of contemporary bioprostheses.