Asunto(s)
Granuloma Letal de la Línea Media/inmunología , Inmunoglobulina G/inmunología , Adulto , Femenino , Fibrosis/inmunología , Fibrosis/patología , Granuloma Letal de la Línea Media/patología , Humanos , Inflamación/inmunología , Inflamación/patología , Masculino , Persona de Mediana Edad , Células Plasmáticas/patologíaRESUMEN
OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCA) binding to neutrophil elastase (NE) and proteinase 3 (PR3) are detectable in most patients with cocaine-induced midline destructive lesions (CIMDL), but the pathogenic role and antigen specificity of these antibodies are unknown. This study was undertaken to assess the effects of NE ANCA on the enzymatic activity of NE, to determine whether these antibodies interfere with the physiologic effect of secretory leukoprotease inhibitor (SLPI), and to investigate the antigen specificity of both NE and PR3 ANCA in patients with CIMDL. We also compared the binding of PR3 ANCA in patients with CIMDL with that in patients with Wegener's granulomatosis (WG). METHODS: PR3 ANCA and NE ANCA were detected by capture enzyme-linked immunosorbent assays (ELISAs) and by indirect immunofluorescence. IgG was purified from the patients' sera, and the influence of NE ANCA on the enzymatic activity of NE and on the inhibitory activity of SLPI was investigated by determining the hydrolysis of N-methoxysuccinyl-Ala-Ala-Pro-Val p-nitroanilide by NE. RESULTS: IgG from NE ANCA-positive sera of patients with CIMDL inhibited the enzymatic activity of NE and did not interfere with the activity of SLPI. In contrast to the findings in WG sera, measurement of PR3 ANCA in CIMDL sera showed only fair to moderate concordance between the 2 different capture ELISAs. Cross-inhibition experiments demonstrated that NE ANCA and PR3 ANCA represent distinct autoantibodies in patients with CIMDL. CONCLUSION: The functional effects of NE ANCA on the enzymatic activity of NE or on the activity of SLPI cannot be implicated in the pathogenesis of CIMDL. The autoimmune reaction that targets neutrophil serine proteases in patients with CIMDL is frequently directed against more than one antigen. The ANCA response, including the reactivity of PR3 ANCA, in patients with CIMDL differs from what has been described in patients with WG.
Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Autoanticuerpos/sangre , Trastornos Relacionados con Cocaína/complicaciones , Granuloma Letal de la Línea Media/etiología , Granuloma Letal de la Línea Media/inmunología , Elastasa de Leucocito/inmunología , Mieloblastina/inmunología , HumanosRESUMEN
PURPOSE: Nasal T/NK lineage lymphoma, previously known as lethal midline granuloma, is common among Oriental, Native-American, and Hispanic patients and is invariably associated with Epstein-Barr virus. Nasal localization, local necrosis, angioinvasion, and aggressive behavior are hallmarks of the disease. Ophthalmologic symptoms and signs may precede lymphoma diagnosis or complicate its disease course. We aim to define the incidence and disease pattern of ophthalmic involvement. DESIGN: Retrospective single-institution consecutive interventional case series. METHODS: Records of all lymphoma patients from 1996 to 2000 were retrieved from a computer database, and the primary sites and lineage were reviewed. Nasal T/NK lymphoma was defined by a combination of morphology, positive CD3 epsilon and CD56 expression, in situ hybridization staining for Epstein-Barr virus expressed RNA (EBER), and negative staining for B cell markers (CD20 and CD79a). RESULTS: Thirty-five consecutive patients with T/NK lymphoma were identified. Primary nasal or nasopharyngeal disease was found in 24 patients. Six (25%) of the 24 patients suffered from vision-threatening complications of two distinct categories, namely uveitis/vitritis and orbital infiltration. The former preceded the diagnosis of lymphoma in two patients and also led to novel ocular complications like rhegmatogenous retinal detachment and macular hole that were successfully managed by ocular surgery. In four patients, orbital extension of lymphomatous disease accompanied biopsy-proven in-field disease relapse. Generally, the prognosis is grave, but remission can still be achieved with aggressive combined chemotherapy and radiotherapy. CONCLUSION: Both oncologists and ophthalmologists should be aware of ocular complications when dealing with known or suspected cases of T/NK lymphoma at diagnosis and relapse. Regular ophthalmic assessment of these patients is warranted.
Asunto(s)
Complejo CD3 , Neoplasias del Ojo/etiología , Granuloma Letal de la Línea Media/complicaciones , Células Asesinas Naturales/patología , Linfoma de Células T/complicaciones , Neoplasias de los Senos Paranasales/complicaciones , Proteínas Ribosómicas , Trastornos de la Visión/etiología , Adulto , Anciano , Antígeno CD56/inmunología , Neoplasias del Ojo/inmunología , Neoplasias del Ojo/secundario , Femenino , Granuloma Letal de la Línea Media/inmunología , Granuloma Letal de la Línea Media/patología , Humanos , Hibridación in Situ , Células Asesinas Naturales/inmunología , Metástasis Linfática , Linfoma de Células T/inmunología , Linfoma de Células T/patología , Masculino , Persona de Mediana Edad , Neoplasias de los Senos Paranasales/inmunología , Neoplasias de los Senos Paranasales/patología , Proteínas de Unión al ARN/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Estudios Retrospectivos , Trastornos de la Visión/diagnóstico , Trastornos de la Visión/inmunologíaRESUMEN
One hundred and twenty-two cases of midline malignant reticulosis (MMR) were studied. A series of antibodies including anti-LCA, UCHL-1, L26, CD45R, and anti-lysozyme were used on paraffin sections by ABC and PAP methods. The results were as follows: 112 cases exhibiting T-cell origin, 4 cases showing B-cell origin, and 6 cases being of uncertain lineage. This result is in accordance with the point of view that most of MMR are T cell lymphoma. Two histological types were classified: sarcomatoid type and granulomatoid type. By using image analyzer, the sarcomatoid type was subdivided into small, medium and large cell types. Sixty-two cases with follow-up data were collected for clinicopathologic analysis. One-year and five-year survival rates in cases with different histologic types were compared and statistically analysed. The results showed that the prognosis was closely related to the histological type.
Asunto(s)
Granuloma Letal de la Línea Media/patología , Antígenos Comunes de Leucocito/análisis , Linfoma de Células T/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Estudios de Seguimiento , Granuloma Letal de la Línea Media/inmunología , Humanos , Inmunohistoquímica , Linfoma de Células T/inmunología , Masculino , Persona de Mediana Edad , Tasa de SupervivenciaRESUMEN
Extranodal non-Hodgkin's lymphoma in the head and neck, especially T-cell lymphoma of the lethal midline granuloma (LMG) type, has unique clinical and histologic features differentiating it from other lymphomas. The authors measured soluble intercellular adhesion molecule-1 (ICAM-1) in sera from 12 patients with T-cell lymphoma of the LMG type and from 52 patients with other head and neck non-Hodgkin's lymphomas, by double-determinant immunoassay. The expression of ICAM-1 in lymphoma tissue was examined in 26 patients by the avidin-biotin immunoperoxidase method. The serum ICAM-1 levels were significantly higher in T-cell lymphoma of the LMG type than in other head and neck lymphomas or in healthy adult controls. Elevated levels of serum ICAM-1 were associated with increased levels of serum lactate dehydrogenase, poor prognosis, and impaired T-cell-dependent immune functions, both in T-cell lymphoma of the LMG type and in other head and neck lymphomas. When we monitored serum ICAM-1 levels in individual patients, the level decreased in the complete remission interval compared to before treatment and went up again when the lymphoma relapsed. Although the staining intensities of ICAM-1 in lymphoma cells were not related to serum ICAM-1 levels, a markedly intense expression of ICAM-1 was found on the angiocentric or angiodestructive lymphoreticular infiltrate region in the tissues from T-cell lymphoma of the LMG type. A higher serum ICAM-1 level and its tissue expression in T-cell lymphoma of the LMG type may be one of the clues to understanding this particular lymphoma. The serum ICAM-1 level could be an efficient parameter for monitoring the clinical course of head and neck non-Hodgkin's lymphomas.
Asunto(s)
Granuloma Letal de la Línea Media/inmunología , Molécula 1 de Adhesión Intercelular/sangre , Linfoma no Hodgkin/inmunología , Neoplasias de los Senos Paranasales/inmunología , Adulto , Anciano , Antígenos CD4/sangre , Antígenos CD8/sangre , Femenino , Granuloma Letal de la Línea Media/patología , Humanos , L-Lactato Deshidrogenasa/sangre , Linfoma no Hodgkin/patología , Masculino , Persona de Mediana Edad , Nariz/patología , Neoplasias Nasales/inmunología , Neoplasias Nasales/patología , Neoplasias de los Senos Paranasales/patología , Senos Paranasales/inmunología , Senos Paranasales/patologíaAsunto(s)
Granuloma Letal de la Línea Media/patología , Linfoma de Células T/patología , Neoplasias Nasales/patología , Antígenos de Neoplasias/inmunología , Citometría de Flujo , Granuloma Letal de la Línea Media/diagnóstico , Granuloma Letal de la Línea Media/inmunología , Herpesvirus Humano 4/inmunología , Humanos , Inmunohistoquímica , Hibridación in Situ , Linfoma de Células T/diagnóstico , Linfoma de Células T/inmunología , Masculino , Persona de Mediana Edad , Neoplasias Nasales/diagnóstico , Neoplasias Nasales/inmunologíaRESUMEN
BACKGROUND: Polymorphic reticulosis, a type of lethal midline granuloma (LMG), has been referred to as nasal T-cell lymphoma (NTL) because of its proliferating cells' positive reactivity to anti-T-lymphocyte antibodies. Recently, several studies have suggested that proliferating cells in NTL may be natural killer (NK) in nature. NK cells and human nonmajor histocompatibility-restricted cytotoxic T-lymphocytes have the morphology of large granular lymphocytes (LGL) (i.e., a high cytoplasmic:nuclear ratio and cytoplasmic granules). Whether NTL-LMG possesses an LGL morphology is examined in this study. METHODS: Two lymph node smears, peripheral blood showing a leukemic picture, and an electron microscope (EM) examination of a cutaneous lesion, respectively, were obtained from four patients with NTL-LMG. Immunohistochemical examination of the proliferating cells and of the Epstein-Barr virus (EBV) genome by both polymerase chain reaction and in situ hybridization also were performed. RESULTS: All patients presented with necrotic and granulomatous lesions in the upper respiratory tract. Histology showed polymorphous cellular infiltrates containing large atypical cells with positive reaction to CD3 (three patients), CD43 (two patients), CD45RO (two patients), and OPD4 (one patient). Imprint smears revealed azurophilic large membrane-delimited granules in an ample cytoplasm, which was confirmed by EM. The presence of the EBV genome in the tumor cells was observed in one patient. CONCLUSION: The current findings showed that NTL-LMG or polymorphic reticulosis is a proliferation of LGL with a CD3+ phenotype.
Asunto(s)
Complejo CD3/metabolismo , Enfermedades Linfáticas/patología , Linfocitos T/patología , Adulto , Secuencia de Bases , Femenino , Genoma Viral , Granuloma Letal de la Línea Media/inmunología , Granuloma Letal de la Línea Media/patología , Granuloma Letal de la Línea Media/virología , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Inmunohistoquímica , Inmunofenotipificación , Hibridación in Situ , Enfermedades Linfáticas/inmunología , Enfermedades Linfáticas/virología , Linfoma de Células T/inmunología , Linfoma de Células T/patología , Linfoma de Células T/virología , Masculino , Microscopía Electrónica , Persona de Mediana Edad , Datos de Secuencia Molecular , Neoplasias Nasales/inmunología , Neoplasias Nasales/patología , Neoplasias Nasales/virología , Reacción en Cadena de la Polimerasa , Linfocitos T/inmunología , Linfocitos T/virologíaRESUMEN
So-called lethal midline granuloma is of great clinical and theoretical interest. The etiology of lethal midline granuloma is unknown and the pathogenesis is variable, with debate as to precise classification and natural history. In this study, we reported genotypic and immunopathological features in 3 cases of lethal midline granuloma. The histopathological diagnosis of their biopsy specimens was initially polymorphic reticulosis/midline malignant reticulosis. Immunohistologic study of the specimens revealed that immature or atypical cells had phenotypes of T-cells, CD2, CD3, CD4 (Case 1), CD4 (Case 2), and CD2, CD3 (Case 3). Those cells were also found to be positive for HLA-DR, which indicated that they were activated T-cells. Immunohistology in T-cells, however, was not able to give a similar clue to clonarity as it was possible within B-cell neoplasms by immunophenotyping the light chains. With the establishment of cDNA probes for the T-cell receptor genes it was possible to analyze neoplasms of lymphocyte origin for lineage and clonality. The Southern blot analysis of 3 cases showed rearrangement of TCR gene, TCR beta and TCR gamma chain (Cases 1 and 2) and TCR beta and TCR delta chain (Case 3), whereas none of them showed rearrangement of immunoglobulin heavy chain. These findings represented conclusive evidence for a monoclonal T-cell proliferation within lethal midline granuloma. On the ground of immunohistological and genotypic studies, lethal midline granuloma histologically diagnosed as polymorphic reticulosis/midline malignant reticulosis are proven to be a T-cell lymphoproliferative disorder.
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Genotipo , Granuloma Letal de la Línea Media/diagnóstico , Receptores de Antígenos de Linfocitos T/genética , Adulto , Anciano , Antígenos CD/análisis , Southern Blotting , Sondas de ADN , Femenino , Reordenamiento Génico , Granuloma Letal de la Línea Media/genética , Granuloma Letal de la Línea Media/inmunología , Antígenos HLA-DR/análisis , Humanos , Masculino , Persona de Mediana EdadRESUMEN
This article presents a case of lethal midline granuloma on the palate of a 44-year-old woman, which had been identified histologically as B-cell lymphoma with leukemic transformation in the terminal stages. At the first visit, physical and laboratory examinations showed no remarkable findings except for a necrotizing ulcer of the palate, and the biopsy specimens only showed massive inflammatory cell infiltration and necrosis of the granulation tissue. There was a short-term resolution after treatment with cyclophosphamide and prednisolone, but the disease reactivated and the necrotic ulcerative lesion progressively advanced into the nasal cavity. Specimens from the third biopsy exhibited histologic features that were consistent with malignant lymphoma of the diffuse, mixed B-cell type. Chemotherapy with the regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone was adopted but was interrupted after a short time because of bone marrow suppression. Subsequently, large numbers of enlarged abnormal lymphocytes with a few vacuoles in the cytoplasm appeared in the circulating blood, indicating leukemic transformation of the midline lymphoma. The patient died on the seventh day after the initiation of chemotherapy. In the presentation of this case, the authors mention clinically important matters regarding midline lethal lymphoma and briefly discuss the pathophysiology and pathogenesis.
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Transformación Celular Neoplásica/patología , Granuloma Letal de la Línea Media/patología , Leucemia/patología , Linfoma de Células B/patología , Adulto , Anticuerpos Monoclonales/biosíntesis , Anticuerpos Monoclonales/inmunología , Antígenos de Neoplasias/fisiología , Coagulación Sanguínea , Femenino , Granuloma Letal de la Línea Media/inmunología , Granuloma Letal de la Línea Media/microbiología , Herpesvirus Humano 4/inmunología , Humanos , Linfoma de Células B/inmunología , Linfoma de Células B/microbiologíaAsunto(s)
Granuloma Letal de la Línea Media/inmunología , Linfoma de Células T/inmunología , Adulto , Antígenos CD/inmunología , Dermatosis Facial/genética , Dermatosis Facial/inmunología , Dermatosis Facial/patología , Neoplasias Faciales/genética , Neoplasias Faciales/inmunología , Neoplasias Faciales/patología , Femenino , Genotipo , Granuloma Letal de la Línea Media/genética , Granuloma Letal de la Línea Media/patología , Humanos , Inmunofenotipificación , Linfoma de Células T/genética , Linfoma de Células T/patología , Masculino , Persona de Mediana EdadRESUMEN
Malignant centrofacial granuloma (MCFG) is a clinical entity characterized by a relentless ulceration of the upper airway involving the nose, palate, and face, without any demonstrable etiology. The origin of 11 cases were analyzed with the help of cell-surface immunostaining in all and with T-cell receptor gene (TCR) rearrangement in 3. The results show that most of the cases of MCFG are in fact T-cell lymphomas with cell-surface antigens (CD2, CD7, CD3) consistent with either early or mature T lymphocytes. However, some cases exhibit B-lymphoid (CD19, CD20) or histiomonocytic (CD13, CD14) lineage-specific markers. In conclusion, despite its remarkable clinical unity, MCFG is a heterogeneous group of neoplastic diseases, most but not all of which may be classified as T-cell lymphoma.
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Granuloma Letal de la Línea Media/genética , Antígenos CD/análisis , Antígenos de Superficie/análisis , Diferenciación Celular , Reordenamiento Génico , Granuloma Letal de la Línea Media/clasificación , Granuloma Letal de la Línea Media/inmunología , Humanos , Linfoma de Células T/clasificación , Linfocitos T/inmunologíaRESUMEN
The lethal midline granuloma is a clinical entity characterized by a relentless ulceration of the upper airway involving the nose, the palate and the face, without any demonstrable etiology. We have applied the cell membrane immunostaining techniques to twelve cases. According to the results, it seems that most of the cases are in fact T-cell lymphomas with membrane staining consistent with either precursor or mature lymphoid T-cells. Some cases, however, exhibit an immunostaining pattern compatible with other origins, the proliferating cells belonging either to the B lymphoid or to the histio-monocytic lineages. We conclude that the lethal midline granuloma is an heterogeneous group of neoplastic diseases, in the most part close to a T cell lymphoma, but with a remarkable clinical unity.
Asunto(s)
Granuloma Letal de la Línea Media/inmunología , Linfocitos T , Granuloma Letal de la Línea Media/patología , Humanos , Técnicas Inmunológicas , Linfoma/inmunologíaRESUMEN
A 60-year-old man affected by nonhealing midline granuloma (NHmG) is described. The histopathological features, the clinical course and the radiosensitivity of the lesion clearly differentiate this pathological condition from malignant lymphomas and from Wegener's granulomatosis (WG). The presence of antinuclear antibodies with an antinucleolar pattern in a subject bearing HLA-B8 suggests the involvement of autoimmune phenomena and a close relation between NHmG and WG.
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Granuloma Letal de la Línea Media/inmunología , Anticuerpos Antinucleares/análisis , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/patología , Granuloma Letal de la Línea Media/patología , Antígenos HLA/análisis , Humanos , Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Cicatrización de HeridasRESUMEN
Three cases of so-called lethal midline granuloma were studied immunologically, using monoclonal antibodies against T cell subsets, and electron microscopically. Immunofluorescence and immunoperoxidase studies of their surgical and autopsy specimens proved that the tumor cells showed positive stainings with anti-Leu 1 and anti-Leu 3a antibodies, and negative staining with anti-Leu 2a, anti-HLA-DR, and anti-immunoglobulin antibodies. These data might indicate that the tumor cells of the three cases had a similar surface antigen phenotype to that of peripheral helper-inducer T cells. The histopathological and ultrastructural examinations of the tumors showed general characteristics reported for T cell lymphomata derived from peripheral T cells.
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Anticuerpos Monoclonales , Neoplasias Faciales/inmunología , Granuloma Letal de la Línea Media/inmunología , Linfoma/inmunología , Linfocitos T , Adulto , Antígenos de Diferenciación de Linfocitos T , Antígenos de Superficie/inmunología , Neoplasias Faciales/patología , Femenino , Técnica del Anticuerpo Fluorescente , Granuloma Letal de la Línea Media/patología , Antígenos HLA-DR , Antígenos de Histocompatibilidad Clase II , Humanos , Linfoma/clasificación , Linfoma/patología , Masculino , Persona de Mediana EdadRESUMEN
A case of Stewart type, non-healing nasal granuloma complicated by dissemination to meninges, peripheral nerve and muscle is described. The deposition of IgA in renal glomeruli in this condition is documented and the significance of this finding is discussed.
Asunto(s)
Granuloma Letal de la Línea Media/patología , Neoplasias Nasales/patología , Anciano , Granuloma Letal de la Línea Media/inmunología , Humanos , Inmunoglobulina A/análisis , Glomérulos Renales/inmunología , Masculino , Meninges/patología , Músculos/patología , Neoplasias Nasales/inmunología , Nervios Periféricos/patologíaRESUMEN
Recent advances in immunology have revealed that the "histiocytic" lymphoma of Rappaport is a proliferation of transformed lymphocytes rather than true histiocytes, and that the malignant cells in malignant histiocytosis (MH) are truly transformed histiocytes. We previously reported cases of MH presenting as lethal midline granuloma (MH-LMG) utilising fresh tissue specimens for the detection of cytological markers in a small number of cases. The results showed the true histiocytic nature of the proliferating cells. In this study, paraffin-embedded specimens from 16 cases with MH-LMG were processed for immunoperoxidase procedures to confirm the true histiocytic nature of the proliferating cells. Five cases with nasal and paranasal lymphomas (ML) were also stained to test the usefulness of immunoperoxidase procedures for distinguishing the MH-LMG from ML. Results were as follows; proliferating cells in MH-LMG were histiocytic in nature, staining positive for lysozyme in MH-LMG in contrast to the negative staining in ML.
Asunto(s)
Granuloma Letal de la Línea Media/patología , Enfermedades Linfáticas/patología , Neoplasias Nasales/patología , Adolescente , Adulto , Anciano , División Celular , Femenino , Granuloma Letal de la Línea Media/inmunología , Histiocitos/patología , Humanos , Técnicas para Inmunoenzimas , Enfermedades Linfáticas/inmunología , Linfoma/patología , Masculino , Persona de Mediana EdadRESUMEN
Midline granuloma and Wegener's granulomatosis are thought to be variants of the same disease. We report studies on a patient with midline granuloma over a 14-month period from the presentation of the disease, in whom a raised serum IgE concentration and a depressed NBT test value were found. These parameters fluctuated with the course of the disease. In addition, a high percentage of IgE positive plasma cells were found in two different sites of the disease. These findings suggest that the aetiology of midline granuloma may be related to hypersensitivity with a concurrent depression in the functional capacity of neutrophils.