Biomedical subjects
J A Goeken
Publications and source records attributed to J A Goeken.
Granulomatous mycosis fungoides. Clinicopathologic study of two cases.
Granulomatous mycosis fungoides is a rare form of mycosis fungoides with controversial histogenesis. Early reports seemed to indicate a favorable prognosis for these patients. We report two cases of granulomatous mycosis fungoides, both of which had other unusual clinical features. The cases were studied with routine light microscopy, immunohistochemistry, electron microscopy, and gene probe studies. Despite some clinical and histopathologic similarities, the results of the immunohistochemical and molecular biologic studies were diverse. These results suggest that granulomatous mycosis fungoides does not define a single subset of cases, immunophenotypically or biologically.
Antineutrophil cytoplasmic antibody--a useful serological marker for vasculitis.
Systemic necrotizing vasculitides, including polyarteritis nodosa, Churg-Strauss syndrome, "overlap" systemic vasculitis, Wegener's granulomatosis, and idiopathic crescentic glomerulonephritis, are frequent clinical diagnostic problems. These diseases have diverse presentations and are often rapidly progressive, causing irreversible injury to the vessels of the kidneys and lungs before effective immunosuppressive therapy is instituted. Even in their less fulminant forms, they are a cause of significant morbidity and mortality. Antineutrophil cytoplasmic antibody, a recently identified autoantibody, has a high sensitivity and specificity for this spectrum of diseases. The clinical and pathological similarities, the high frequency of antineutrophil cytoplasmic antibody expression, and the similar good response to immunosuppressive therapy suggest that these diseases may be linked by a common pathophysiological mechanisms. Evidence is growing that antineutrophil cytoplasmic antibody plays a central role in this mechanisms. A revision in the classification scheme of vasculitides to recognize that the polyarteritis group (polyarteritis nodosa, Churg-Strauss syndrome, and "overlap" systemic vasculitis), Wegener's granulomatosis, and idiopathic crescentic glomerulonephritis are closely related diseases may be warranted. The clinical and pathological features of systemic necrotizing vasculitides and the current knowledge concerning antineutrophil cytoplasmic antibodies are reviewed.
Activated CD-8 cells and HLA DR expression in alcoholics without overt liver disease.
Lymphocytes from alcoholics without liver disease were immunophenotyped by flow cytometry immediately after admission for detoxication and again after 4 to 10 days of abstinence. We found a small but significant elevation of T lymphocytes at admission compared to controls and decreases in the numbers of B cells and natural killer cells in many patients. A significant elevation of activated T cells was confirmed. The ratio of activated T cells to activated non-T cells was also substantially increased, but declined slightly during early withdrawal. The increase in activated T cells was due mostly to increased numbers of activated CD8hi cells. These activation changes did not revert toward normal as quickly as the other changes and may represent an indication of immune damage at a preclinical stage. An additional finding of interest was a substantial decrease in the expression of HLA DR on CD4+ and non-T cells. The significance of this decrease is not known, but we speculate that it may result in a decline in the efficiency of antigen presentation.
Clonal immunoglobulin gene rearrangement in the infarcted lymph node syndrome.
The authors report a case of complete lymph node infarction in which a specific etiology could not be determined by morphologic or immunophenotypic studies; however, clonal rearrangement of the immunoglobulin gene was demonstrated by Southern blot hybridization of DNA extracted from the necrotic tissue. A subsequent lymph node biopsy later was diagnosed as malignant lymphoma, using morphologic, immunophenotypic and genotypic criteria. Identical clonally rearranged bands were present in DNA from both the infarcted nodal and the subsequent tissue biopsies. In the setting of lymph node necrosis, gene rearrangement studies may provide diagnostic information concerning clonality, even if morphologic and immunophenotypic studies are indeterminate for a lymphoproliferative process.
Cutaneous angiomyolipoma. A light-microscopic, immunohistochemical, and electron-microscopic study.
We report a case of cutaneous angiomyolipoma found on the helix of a 67-year-old man. The lesion was studied by routine light microscopy, special stains, immunohistochemical methods, and electron microscopy. Histologic examination showed a well-circumscribed nodule in the dermis composed of an intimate mixture of blood vessels, smooth muscle, and mature fat. These components were confirmed by special stains, immunohistochemistry, and electron microscopy. We concluded that the unique features of this lesion distinguish it from other lesions such as angiomyoma, angiolipoma, and other mixed mesenchymal tumors. This report demonstrates that the features considered diagnostic of angiomyolipoma can occur in extrarenal sites and, therefore, this diagnosis cannot be excluded on the basis of site alone.
Establishment of a reference interval for beta 2-microglobulin in cerebrospinal fluid with use of two commercial assays.
Increased concentrations of beta 2-microglobulin in cerebrospinal fluid have been used to detect central nervous system involvement with metastatic cancer and with neurological complications of AIDS. However, no adequate reference interval study has been reported for beta 2-microglobulin in cerebrospinal fluid. We established a reference interval with both the Abbott IMx microparticle enzyme-linked immunoassay (EIA) (0.6-2.0 mg/L) and the Pharmacia beta 2-micro EIA 96 method (0.8-2.2 mg/L) for beta 2-microglobulin in cerebrospinal fluid. The two methods correlate well, with the latter method giving slightly higher values. beta 2-Microglobulin increases with age in adults by about 0.1 mg/L every 7.5 years, with no significant difference between genders.
Ocular manifestations of patients with circulating antineutrophil cytoplasmic antibodies.
Antineutrophil cytoplasmic antibodies are seen in patients with systemic vasculitides, especially Wegener's granulomatosis. Antineutrophil cytoplasmic antibodies are helpful laboratory markers for these disease. We report on the ocular findings of six patients with systemic vasculitis who had antineutrophil cytoplasmic antibodies. Four patients had systemic Wegener's granulomatosis, one had microscopic polyarteritis, and in one a specific histopathologic diagnosis could not be made. Two patients were first evaluated for systemic vasculitis because of their ocular manifestations. Ocular findings included ptosis, bilateral lacrimal gland masses, proptosis, choroidal folds, episcleritis, phlebitis, retinal and vitreous hemorrhage, keratitis sicca, and bilateral central scotomas. It was difficult to make a systemic diagnosis in all cases. If systemic vasculitis is in the differential diagnosis of a patient with suggestive ocular findings, antineutrophil cytoplasmic antibody testing should be considered. A prospective study of antineutrophil cytoplasmic antibody testing should be considered in patients with ocular findings that suggest the possibility of vasculitis.
Kappa immunoglobulin light chain gene rearrangement in a T-lineage chronic lymphocytic leukemia.
Until recently, only B-lineage lymphoid cells were observed to rearrange kappa immunoglobulin light chain genes. The authors examine peripheral blood mononuclear cells from a patient with chronic lymphocytic leukemia. More than 90% of these cells bound T-lymphocyte specific antibodies, failed to bind B-lymphocyte specific antibodies, had rearranged T-cell receptor beta-chain genes and had retained immunoglobulin heavy chain genes in the germline configuration. Despite these T-lineage markers, the majority of these cells had rearranged kappa immunoglobulin light chain genes. This provides the first conclusive evidence for rearranged kappa genes in malignant T-lineage cells and warns that gene rearrangement studies alone cannot indicate tumor cell lineage. To detect T-lineage cells that rearrange immunoglobulin genes, multiple immunophenotypic and genotypic parameters must be evaluated. These cells may provide important models to study how normal and malignant cells rearrange lymphocyte receptor genes.
Clonal immunoglobulin gene rearrangement in nodular lymphoid hyperplasia of the gastrointestinal tract associated with common variable immunodeficiency.
The authors report a case of common variable immunodeficiency associated with nodular lymphoid hyperplasia of the gastrointestinal tract in which a clonal population of lymphoid cells was detected by immunophenotypic and genotypic studies on tissue obtained by colonoscopic biopsy. The patient has been followed up for more than 50 months without clinical, radiographic, or pathologic evidence of lymphoma. The significance of clonal rearrangement in the setting of immunodeficiency and the role of genotypic studies in defining lymphoid malignancy are discussed.
The diagnostic utility of immunophenotyping and immunogenotyping in the pathologic evaluation of lymphoid proliferations.
One hundred eighty-two specimens of suspected lymphoma and lymphocytic leukemia were examined by morphology, immunophenotype, and immunogenotype (genotype) in order to answer the following questions: How often and in what situations does immunophenotyping help resolve a diagnostic problem that is not resolved by morphology? How frequently does genotyping help resolve a diagnostic problem that is not resolved by morphology and immunophenotyping? Of 182 cases for which fresh tissue was available, sixty-five cases were considered morphological diagnostic problems: There were 32 cases of neoplasia versus non-neoplastic proliferation, 16 cases of neoplasia with undifferentiated or ambiguous morphology, and 17 cases of lymphoma or lymphocytic leukemia with an uncertain subtype. Immunophenotyping helped to resolve 33 of these 65 cases. Of the remaining 32 cases genotyping helped to resolve the diagnosis in 16. These results suggest that immunophenotyping may diagnose approximately 50% of those cases which present a morphological problem, and that genotyping is also helpful in a limited but significant number of problem cases.
Immunophenotypic and genotypic characterization of primary non-Hodgkin's lymphoma of the gastrointestinal tract.
Antigen receptor gene rearrangement studies have been applied to gastrointestinal (GI) lymphoid proliferations in only a limited number of cases, and their use and contribution to the diagnosis and characterization of GI lymphomas is unknown. We retrospectively studied 17 cases of primary GI lymphoma using fresh/frozen tissue with a combination of immunophenotypic and genotypic techniques. The vast majority of the neoplasms were B-cell lymphomas (88%) with rare T-cell tumors. The most common B-cell immunophenotype was IgM-kappa (40%), while five of the B-cell lymphomas (33%) lacked surface light chain immunoglobulin. Immunophenotypic evidence of histiocytic differentiation was not identified. Clonality was confirmed in 59% (10/17) of the neoplasms by immunophenotyping and 88% (15/17) by antigen receptor gene rearrangement studies. All of the 15 B-cell lymphomas (100%) demonstrated clonally rearranged immunoglobulin gene rearrangement. The two lymphomas with T-cell immunophenotypes did not demonstrate T-cell receptor beta-chain gene rearrangement. Antigen receptor gene rearrangement data can be useful and may even be necessary in certain cases for the proper classification and/or diagnosis of GI lymphoid proliferations.
Sarcoidlike granulomas with angiitis may not be sarcoidosis.
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Temporal artery biopsies. Correlation of light microscopy and immunofluorescence microscopy.
Immunopathologic studies are done routinely on biopsy specimens from tissues affected by many autoimmune diseases. To evaluate the role of direct immunofluorescence microscopy (DIFM) in identifying temporal arteritis, the authors reviewed all temporal artery biopsies done over a 30-month period (100 consecutive biopsies). The DIFM, using antibodies to IgG, IgM, IgA, complement, and fibrinogen, had a diagnostic sensitivity rate of 93% and a specificity rate of 87% compared with light microscopy. In biopsy specimens showing arteritis by light microscopy, IgG was demonstrated by DIFM in 85% of cases, IgM in 69%, and IgA in 15%. In one patient, a DIFM staining pattern highly suspicious of temporal arteritis identified a patient with features of clinical temporal arteritis despite negative findings by light microscopy. The demonstration of immunoglobulin by DIFM supports the possible role of humoral immunity in the pathogenesis of temporal arteritis.
Blast-like cells in cerebrospinal fluid of neonates. Possible germinal matrix origin.
Primitive cell clusters (PCCs) composed of immature blast-like cells were observed in Wright's-stained cerebrospinal fluid (CSF) cytocentrifuge specimens from four infants over an 18-month period. All of these patients had hydrocephalus; in three this was secondary to subependymal germinal matrix intraventricular hemorrhage (IVH) associated with prematurity. The fourth was associated with Arnold-Chiari malformation, Chiari type II. In the CSF samples from the patients with IVH, hemosiderin-laden macrophages were also prominent and, in some cases, were intimately admixed with the PCCs. Immunoperoxidase staining of cytocentrifuge preparations from one of the patients revealed that the PCCs stained with neuron-specific enolase (NSE) but not with pan-leukocyte antibodies. Cells with similar morphologic characteristics to PCCs in the CSF of infants have been infrequently illustrated in the literature and thought to be of hematopoietic origin. However, the immunohistochemical findings and the clinical presentation suggest that PCCs are most likely germinal matrix cells.
Hyaline cells in chondroid syringomas. A light-microscopic, immunohistochemical, and ultrastructural study.
The origin and significance of hyaline cells (HC) in chondroid syringomas (CS) is unclear. In a review of 20 CS, we found HC in eight cases. These were studied immunohistochemically, using antibodies to cytokeratin, vimentin, carcinoembryonic antigen, epithelial membrane antigen, desmin, muscle-specific actin, S-100 protein, myoglobin, alpha-1-antitrypsin, chromogranin, glial fibrillary acidic protein, and neuron-specific enolase. HC gave a positive reaction to cytokeratin, vimentin, S-100 protein, and neuron-specific enolase, but not to the other antibodies. Thioflavin-T stain for amyloid was negative. Ultrastructurally, HC contained intermediate filaments in hap-hazard arrangement without specific structures or densities, and had sparse intracytoplasmic organelles and rare desmosomal attachments. Intermediate forms between epithelial cells and HCs were also identified. Our results suggest that HCs are relatively common in Cs (40%) and are more frequent in CS with solid nests and myxoid stroma (relative frequency 62.5%). Immunohistochemically, HCs of CS have a specific phenotype profile; however, ultrastructurally, HCs of CS are not distinct and are similar to HCs in other organs. These results do not suggest an exclusive myoepithelial origin of HCs; it appears that HCs could derive from any epithelial cell type of sweat glands, probably via a regressive process.
Epstein-Barr virus-related lymphoproliferative disorders following bone marrow transplantation: an immunologic and genotypic analysis.
Four patients from 1.5 to 18 yr of age who had received partially matched T-cell-depleted bone marrow transplants for acute leukemia succumbed to a widespread lymphoproliferative disorder (LPD) at 56 to 147 days after transplant. Premortem diagnosis of LPD was suggested in two because plasmacytoid cells were observed in the blood and bone marrow, and in the cerebrospinal fluid of one of these patients. Serum clonal immunoglobulins (Igs) were also demonstrated in these two patients premortem, while the other two had clonal Igs in serum obtained at autopsy. Autopsies revealed a plasmacytoid infiltrate or immunoblastic lymphoma involving lymph nodes, spleen, liver, lungs, gastrointestinal tract, and kidneys. Immunoglobulin gene rearrangement studies performed in three revealed B-cell clonality. Both immunohistochemical and DNA gene rearrangement studies were useful in differentiating the LPD from the pretransplant leukemia. Epstein-Barr virus (EBV) genome was found in the tissues of the three patients studied. The diagnosis of EBV-induced LPD must be considered in bone marrow transplant patients who deteriorate and who exhibit serum clonal Igs or prominent plasmacytoid cells in laboratory specimens.
The risk of cytomegalovirus transmission by penetrating keratoplasty.
To investigate the risk of cytomegalovirus transmission by corneal transplantation, we quantitated anticytomegalovirus IgG levels of donor, preoperative, and postoperative serum samples. Of 118 patients, 79 (67%) were seropositive preoperatively. Twenty-five patients who were seronegative preoperatively received a graft from a positive donor and two (8%) seroconverted. Eleven patients who were seronegative preoperatively received a graft from a negative donor and one (9%) seroconverted. None of the patients who seroconverted had a febrile illness and all three grafts were clear.