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.     

Central nervous system coccidioidomycosis: a clinicopathologic study of treatment with and without amphotericin B

The clinical and pathologic findings in 32 patients with central nervous system (CNS) coccidioidomycosis were studied. Seventeen patients had received more than 1.5 g of amphotericin B (AMB), chiefly intravenously, during treatment periods of up to eight years. Eight patients had received 246 mg to 1.3 g of AMB, and three patients had received only brief treatment (one to three days; total dose, no more than 100 mg). Fifteen patients had not received AMB. Significant clinical differences between the patients treated with and without AMB were longer survival time following diagnosis of illness (P less than 0.05) and more frequent cranial nerve signs in the treated patients (P = 0.089). The wide spectrum of macroscopic and microscopic lesions in the CNS included meningitis, ventriculitis, hydrocephalus, and cerebritis. Long-standing infections were associated with disseminated discrete foci of gliosis and infarcts in the brain, particularly in the basal ganglia and deep white matter, related to endarteritis obliterans in basilar meninges. In contrast to patients with CNS and systemic mycoses treated with amphotericin B methyl ester (J Infect Dis 146:125, 1982), no diffuse lesions of white matter were found in patients treated with or without AMB. Histopathologic patterns observed in this study included leptomeningitis alone, leptomeningitis with cerebritis, leptomeningitis with cerebritis and infarcts, and the unusual pattern of disseminated miliary granulomas. The frequency and extent of CNS lesions in the groups treated with and without AMB were not significantly different. It is concluded that AMB therapy, while prolonging survival, does not alter the spectrum of pathologic findings in CNS coccidioidomycosis infection.     

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.     

Radiation-induced changes in the breast

Thirty-six postirradiation breast tissue specimens from 30 patients with breast cancer treated by primary radiation therapy were evaluated to define the effects of therapeutic doses of ionizing radiation on the residual non-neoplastic breast tissue. Breast tissue was sampled an average of 30.4 months after completion of therapy because of the development of new clinically or mammographically detectable abnormalities within the treated breasts. The average radiation dose was 6,399 rad to the primary tumor area and 4,778 rad to the remainder of the breast. Breast tissue sections from 35 nonirradiated patients served as control specimens. The most characteristic radiation effects consisted of atypical epithelial cells in the terminal duct lobular unit ( TDLU ) associated with lobular sclerosis and atrophy. These changes were present in all of the irradiated patients but varied in severity and extent among patients and within individual patients. This variation was not related to the presence or absence of carcinoma elsewhere in the specimen, radiation dose, patient age, time to postirradiation tissue sampling, or use of adjuvant chemotherapy. Epithelial atypia in larger ducts, stromal changes, and vascular changes were less frequent but were always accompanied by prominent TDLU changes. Radiation effects could usually be clearly distinguished from carcinoma involving the TDLU by the absence of both cellular proliferation and distention of the involved TDLU and by the preservation of cellular polarity and cohesion in areas of presumed radiation-induced injury. Familiarity with these changes is of considerable practical importance in that they must be distinguished from new or recurrent neoplasms.     

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.     

Giant cell myocarditis after mitral valve replacement: case report and studies of the nature of giant cells

A 22-year-old man with Marfan's syndrome and a history of antinuclear antibody-positive hepatitis died 25 days after undergoing cardiac valve replacement surgery for mitral valve prolapse. Giant cell myocarditis was found at autopsy. The multinucleated giant cells were shown by immunoperoxidase techniques to contain lysozyme, but not myosin or creatine phosphokinase, suggesting that they were derived from macrophage, rather than myocyte, precursors.     

Immunoblastic sarcoma of T- and B-cell types: morphologic description and comparison

Immunoblastic sarcoma (IBS) is a large cell lymphoma conceptually related to transformed T and B lymphocytes of the extrafollicular compartment of the immune system (immunoblasts). This light microscopic study of a series of 47 immunologically defined cases of IBS was undertaken in an attempt to define more precisely the morphologic features of the T- and B-cell subtypes. A remarkable morphologic spectrum characterized T-IBS (31 cases), which could be divided into two main groups: 1) tumors composed of varying mixtures of small, medium-sized, and large transformed cells; and 2) tumors with more homogeneous populations of medium-sized or large transformed cells. These cells, in all sizes, generally had abundant pale-staining cytoplasm, delicate nuclear membranes, finely dispersed chromatin, and one to several, small or medium-sized, prominent nucleoli. A distinctive background of small, irregular lymphocytes was frequently present. Plasmacytoid differentiation, seen most consistently as amphophilic staining of the cytoplasm, generally characterized B-IBS (16 cases). B-IBS similarly showed a morphologic spectrum that occurred in two main forms: 1) tumors consisting of a spectrum of transformed cells, with the smaller cells often showing the most striking plasmacytoid differentiation; and 2) tumors consisting predominantly of medium-sized to large transformed cells with varying degrees of plasmacytoid differentiation. With this constellation of features, all but two cases of T-IBS and one case of B-IBS were morphologically distinguishable.     

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.     

Ultrastructural localization of immunoglobulins in hairy cell leukemia

Neoplastic cells from 13 cases of hairy cell leukemia were investigated for immunoglobulin production and lysozyme activity by an electron-immunoperoxidase technique. In 10 cases cytoplasmic immunoglobulins were found, but lysozyme activity was absent in all cases. Immunoglobulins were detected in the perinuclear space and endoplasmic reticulum and at the surface of hairy cells. Of the cases in which immunoglobulins were detected in hairy cells, nine were positive with IgM antiserum and one with IgG antiserum. The immunoglobulins were monoclonal in all cases; six were positive with lambda antiserum and three with kappa antiserum. The class and type of surface immunoglobulins were identical to those of cytoplasmic immunoglobulins in the hairy cells. These results support the conclusion that hairy cells are commonly derived from immunoglobulin-producing B cells at an earlier stage of differentiation than plasma cells.     

Primary glomerulonephritis complicating diabetic nephropathy: report of seven cases and review of the literature

Glomerulonephritis has been recognized as a rare complication of diabetes mellitus. The clinical, pathologic, and laboratory findings for 18 diabetic patients were reviewed. Eight of these patients (44 per cent) were found to have primary glomerulonephritis in addition to diabetic nephropathy. Although this series may not represent the true incidence of complicating glomerulonephritis in diabetes, it is probable that the incidence of this condition has been underestimated. An additional 26 previously reported cases are reviewed.     

Inflammatory abdominal aortic aneurysm: report of six cases

Six cases of inflammatory aneurysm of the abdominal aorta are described. All patients were male, aged 59 to 80 years, and five had symptomatic atherosclerotic cerebrovascular or cardiovascular disease. In three the diagnosis of inflammatory aneurysm was suggested preoperatively on the basis of computed tomographic or ultrasonographic scanning. On gross examination the aneurysm wall was about 1 cm thick and included an inner narrow layer of atherosclerotic plaque, which was contiguous with the outer thick fibroinflammatory component. Microscopically, this component consisted of fibroblasts and collagen, which entrapped fat, nerves, and lymph nodes and was infiltrated by lymphocytes and plasma cells. Plasma cells, lymphocytes, and fibroblasts predominated in four patients, while two showed abundant dense collagen with fewer inflammatory cells and fibroblasts. There was associated vasculitis, predominantly phlebitis, in three. Inflammatory aneurysms represent a distinct group of abdominal aortic aneurysms.     

Psychiatric teaching and consultation in a primary care clinic

Basing their report on an 11-month experience as members of a primary care team in an outpatient municipal hospital setting, the authors identify six major presenting problems in consultation requests: functional complaints, noncompliance, depression, chronic psychosis, alcoholism, and physician role conflicts. The primary care physician's multiple roles, the content of general medical practice, and the ambulatory setting all colored these consultation requests and shaped the ways in which psychiatrists could be most helpful as consultants. Consulting psychiatrists should have special expertise in several specific clinical areas that are common in primary care practice. They can help primary physicians become more effective clinically by encouraging them to heighten their personal and interpersonal sensitivities and to think through their own values and beliefs about medical practice.