RESUMEN
Mucor irregularis (Rhizomucor variabilis) infection and lethal midline granuloma (LMG) are characterized by progressive swelling, ulceration, and destruction of the central face that is usually fatal. Pathological features are inflammation, necrosis, and granulation. LMG has been called by various names, and in recent years, it has been known as NK/T cell lymphoma. However, diagnosis still relies on the progressive necrosis course rather than malignancy in histology. The disease has long challenged physicians, particularly when it worsens with radiotherapy or chemotherapy but sometimes achieves total remission without anti-malignancy therapies. We describe a 35-year-old man who had typical clinical-pathological symptoms of LMG, which turned out to be primary M. irregularis infection; that was diagnosed by positive tissue culture and fungal elements in histology. The patient was successfully treated with antifungal therapy (liposomal amphotericin B, total 4,600 mg and amphotericin B total 277 mg, over a duration of 70 days). We hereby review current knowledge about the epidemiology, clinical manifestations, radiographic characteristics, and pathologic features of LMG with those of M. irregularis infection and their associations. We conclude that primary M. irregulars infection can mimic the clinico-pathological symptoms of LMG and the condition responds favorably to aggressive antifungal therapy.
Asunto(s)
Granuloma Letal de la Línea Media/microbiología , Mucor/aislamiento & purificación , Adulto , Antifúngicos/uso terapéutico , Granuloma Letal de la Línea Media/tratamiento farmacológico , Humanos , Masculino , Mucor/genética , Mucor/fisiologíaAsunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Actinomicosis/complicaciones , Actinomicosis/diagnóstico , Granuloma Letal de la Línea Media/diagnóstico , Granuloma Letal de la Línea Media/microbiología , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Actinomicosis/etiología , Adulto , Fármacos Anti-VIH/uso terapéutico , Diagnóstico Diferencial , Granuloma Letal de la Línea Media/radioterapia , Humanos , Masculino , Dosificación Radioterapéutica , Resultado del TratamientoRESUMEN
A 73-year-old man was admitted to our hospital for evaluation of abnormal lung shadows in the left lung. Chest computed tomography revealed a cavitary lesion with irregular edges in the right S10 and a nodular lesion with well-defined margins in the left S6. Histological examination of a specimen obtained by transbronchial lung biopsy revealed squamous cell carcinoma in the right S10 but no significant findings in the left S6. Thirdly, 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) demonstrated that the nodular shadow in the left S6 was a low-uptake structure and that the cavitary lesion in the right S10 was a high-uptake lesion. We therefore considered that the nodular shadow in the left S6 was not one of neoplastic disease. Partial lung resection of the left S6 was carried out by videoassisted thoracoscopic surgery. The pathological diagnosis of the left S6 was epithelial granuloma with caseation. A culture of the same resected specimen was positive for Mycobacterium avium. The eventual clinical staging for the squamous cell carcinoma in the right S10 was cT2N0M0 (IB). Radical surgical treatment and right lower lobectomy were performed for the S10 lesion. We considered that 18F-FDG-PET was an effective noninvasive procedure for diagnosis of solitary or multiple solitary nodular shadows in the lung.
Asunto(s)
Carcinoma de Células Escamosas/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Granuloma Letal de la Línea Media/diagnóstico por imagen , Enfermedades Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Infección por Mycobacterium avium-intracellulare/diagnóstico por imagen , Radiofármacos , Tomografía Computarizada de Emisión , Anciano , Carcinoma de Células Escamosas/complicaciones , Diagnóstico Diferencial , Granuloma Letal de la Línea Media/complicaciones , Granuloma Letal de la Línea Media/microbiología , Humanos , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/microbiología , Neoplasias Pulmonares/complicaciones , Masculino , Complejo Mycobacterium avium/aislamiento & purificación , Infección por Mycobacterium avium-intracellulare/complicaciones , Infección por Mycobacterium avium-intracellulare/microbiologíaRESUMEN
BACKGROUND: Polymorphic reticulosis is one of several diseases constituting lethal midline granuloma (LMG). Previous immunohistochemical studies suggested a T-cell nature of proliferating cells; the term nasal T-cell lymphoma (NTL-LMG) has since been used widely. The authors' previous study in Asian countries showed the clustering of Mongolian patients with NTL-LMG, but the frequency varied with geographic area; it was much higher in Korea and southwest Japan (Okinawa) than in Shanghai and Honshu, Japan. Recently an etiologic role of Epstein-Barr virus (EBV) for the development of NTL-LMG has been postulated. METHODS: In this study, the presence of EBV and human T-cell lymphocytic leukemia virus type 1 (HTLV-1) genomes were examined in NTL-LMG patients from Southwest Japan (Okinawa, 10 patients), another Japanese district (Honshu, 21 patients), and Shanghai, China (5 patients). All of the tissues from different geographic sites were analyzed at one central location. RESULTS: Immunohistochemistry showed that proliferating large cells were positive for CD43 and/or CD45RO, identical with reported NTL-LMG cases. Polymerase chain reaction (PCR) revealed the presence of EBV genome in the NTL-LMG lesions, but the frequency varied according to the geographic area: 67% in Okinawa, 33% in Honshu, and 100% in Shanghai. In situ hybridization provided positive signals in the nuclei of proliferating cells. Expression of latent membrane protein in the proliferating cells of cases positive for EBV by PCR and in situ hybridization was confirmed. CONCLUSIONS: The results suggest that the EBV may play a role in the development of NTL-LMG. However, the variation of frequency of EBV genome in different geographic locations suggests that EBV infection may not be an indispensable condition for the disease.
Asunto(s)
Antígenos CD , Granuloma Letal de la Línea Media/microbiología , Herpesvirus Humano 4/aislamiento & purificación , Linfoma de Células T/microbiología , Neoplasias Nasales/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , China/epidemiología , Femenino , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/epidemiología , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Humanos , Inmunohistoquímica , Japón/epidemiología , Antígenos Comunes de Leucocito/análisis , Leucosialina , Linfoma de Células T/complicaciones , Linfoma de Células T/epidemiología , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Neoplasias Nasales/complicaciones , Neoplasias Nasales/epidemiología , Sondas de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , Sialoglicoproteínas/análisisRESUMEN
Lethal midline granuloma (LMG) is a clinical term used to describe a condition which may be manifested histologically as Wegener's granulomatosis (WG), polymorphic reticulosis (PR), and malignant lymphoma (ML). WG is an inflammatory disease, and PR and ML are considered to represent a neoplastic proliferation of lymphoreticular cells. In this report, twenty-two cases of LMG in Okinawa were examined. The frequency of LMG per 100,000 outpatients of the ear, nose and throat clinic in Okinawa was 67, and the higher frequency of PR (27) and ML (34) in Okinawa than in other districts of Japan was characteristic. Polymerase chain reaction, in situ hybridization, and immunohistochemical studies showed that the proliferating cells in PR were CD43+ and simultaneously contained Epstein-Barr viral genome in their nuclei. The higher frequency of PR and ML in Okinawa is discussed in conjunction with a review of pertinent literature: multiple factors including genetic, viral environmental, and socioeconomic factors seem to affect the frequencies of these diseases.
Asunto(s)
Granuloma Letal de la Línea Media/epidemiología , Adulto , Anciano , Secuencia de Bases , Cartilla de ADN/química , ADN Viral/análisis , Femenino , Granuloma Letal de la Línea Media/microbiología , Herpesvirus Humano 4/genética , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Hibridación in Situ , Japón , Masculino , Persona de Mediana Edad , Datos de Secuencia MolecularRESUMEN
We analysed the terminal repeats of Epstein-Barr virus (EBV) in DNAs isolated from six lethal midline granuloma (LMG) biopsies. A single fused terminal fragment could be detected in each case, indicating that these angiocentric peripheral T cell lymphomas represent clonal proliferations of cells infected with EBV on a single occasion. Using reverse transcriptase-PCR, we detected EBV nuclear antigen (EBNA) 1 and latent membrane protein (LMP) 1, but not EBNA 2 messages in LMG biopsy RNAs. The splicing pattern of the EBNA 1 message was consistent with the usage of a promoter localized in the BamHI F fragment (F promoter). The BamHI W fragment repeats and LMP-coding sequences were highly methylated in all cases. In contrast, the LMP regulatory sequences were found to be hypomethylated or partially methylated, as in LMP-expressing nasopharyngeal carcinomas.
Asunto(s)
Antígenos Virales/análisis , Proteínas de Unión al ADN/análisis , Granuloma Letal de la Línea Media/microbiología , Herpesvirus Humano 4/genética , Linfoma de Células T Periférico/microbiología , Proteínas Oncogénicas Virales/análisis , Proteínas de la Matriz Viral/análisis , Antígenos Virales/genética , Secuencia de Bases , Células Clonales , ADN Viral/genética , Proteínas de Unión al ADN/genética , Antígenos Nucleares del Virus de Epstein-Barr , Femenino , Granuloma Letal de la Línea Media/patología , Infecciones por Herpesviridae/microbiología , Herpesvirus Humano 4/química , Humanos , Linfoma de Células T Periférico/patología , Masculino , Metilación , Datos de Secuencia Molecular , Proteínas Oncogénicas Virales/genética , Reacción en Cadena de la Polimerasa , Secuencias Repetitivas de Ácidos Nucleicos/genética , Transcripción Genética , Infecciones Tumorales por Virus/microbiología , Proteínas de la Matriz Viral/genéticaRESUMEN
Lethal midline granuloma (LMG) is associated with Epstein-Barr virus (EBV). The latter has at least two subtypes with different biological properties. The subtypes can be identified by their genomic configuration. Using EBV-RNA (EBER) in situ hybridization and EBV polymerase chain reaction (PCR), we have looked for the presence of EBV in six LMGs and six non-Hodgkin's lymphomas (NHLs) located in the nasopharyngeal region, and determined the subtype of EBV. Six of six LMGs were positive by PCR and EBER in situ hybridization, whereas NHLs were either negative or, in three of six cases, showed few EBER-positive cells considered to be nonneoplastic lymphocytes. The subtype 2 was found in LMG lesions of three of six patients; the remaining three of six patients with LMG had the generally occurring subtype 1. The results indicate that the association of EBV with NHL may depend more on tumor type than on its localization. The occurrence of the rare subtype 2 in LMG may relate to a covert immune defect.
Asunto(s)
Granuloma Letal de la Línea Media/microbiología , Herpesvirus Humano 4/patogenicidad , Linfoma de Células T/inmunología , Anciano , Secuencia de Bases , Niño , Preescolar , ADN Viral/análisis , Femenino , Genes Virales , Herpesvirus Humano 4/química , Herpesvirus Humano 4/clasificación , Humanos , Inmunofenotipificación , Hibridación in Situ , Masculino , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos/química , Reacción en Cadena de la Polimerasa , Provirus/química , ARN Viral/análisis , Proteínas Estructurales Virales/genéticaRESUMEN
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.
Asunto(s)
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/microbiologíaRESUMEN
A Japanese woman with an 8-year history of lymphomatoid papulosis (LP) had lethal midline granuloma (LMG) develop at the age of 51 years. There were histologic similarities between LP and LMG seen in this patient. Surface phenotypic studies on nasal and cutaneous lesions demonstrated a population of T-cells expressing CD2, CD4, CD25, CD30, and histocompatibility antigen-DR (HLA-DR). Genotypic analyses of nasal and skin biopsy specimens disclosed a clonal rearrangement of the beta T-cell receptor gene with the same rearrangement pattern. These data indicate that this patient had LMG characterized by clonal peripheral T-cell lymphoma, which probably resulted from progression of the LP.
Asunto(s)
Granuloma Letal de la Línea Media/patología , Linfoma de Células T Periférico/patología , Trastornos Linfoproliferativos/patología , Enfermedades de la Piel/patología , Adulto , Biopsia , ADN Viral/análisis , Femenino , Reordenamiento Génico de Linfocito T/genética , Granuloma Letal de la Línea Media/genética , Granuloma Letal de la Línea Media/microbiología , Herpesvirus Humano 4/genética , Humanos , Inmunofenotipificación , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/microbiología , Trastornos Linfoproliferativos/genética , Trastornos Linfoproliferativos/microbiología , Enfermedades de la Piel/genética , Enfermedades de la Piel/microbiologíaRESUMEN
We report 4 cases with neurological disorders due to lethal centrofacial granulomas of unknown origin, and we review the relevant literature. This puzzling disease is characterized by a relentless ulceration of the nose progressing toward the base of the skull, and frequently involving the cranial nerves, the meninges and later the central nervous system. The main clinical point in such situations is to ascertain that no microorganism, no cancer, no specific disease is responsible for the centrofacial lesions, since the microscopic findings may be non-specific. When the entire work-up to exclude all differential diagnoses is completed, the clinician has to deal with lethal centrofacial granuloma. This seems to be a heterogeneous disease, in most of the cases close to malignant T lymphomas. Management is based on radiotherapy, chemotherapy and renutrition with treatment of frequent infectious complications. The prognosis is poor.
Asunto(s)
Granuloma Letal de la Línea Media/complicaciones , Enfermedad de Hodgkin/complicaciones , Enfermedades del Sistema Nervioso/etiología , Adolescente , Adulto , Granuloma Letal de la Línea Media/microbiología , Enfermedad de Hodgkin/microbiología , Humanos , MasculinoRESUMEN
Five cases of lethal midline granuloma were identified histologically and phenotypically as peripheral T-cell lymphomas. Epstein-Barr virus (EBV) DNA was detected in the nasal tumour biopsy specimens by Southern blotting and in-vitro hybridisation with simultaneous detection of EBV-determined nuclear antigen (EBNA) and T-cell surface markers by two-colour immunofluorescence. Further immunofluorescence and northern blotting revealed that EBNA2 gene and also latent membrane protein gene were expressed in the nasal tumour cells. The patients had high titres of antibodies to EBV. These findings suggest that lethal midline granuloma is causally associated with EBV.
Asunto(s)
Proteínas de la Cápside , Granuloma Letal de la Línea Media/microbiología , Herpesvirus Humano 4/aislamiento & purificación , Linfoma/microbiología , Adulto , Anticuerpos Antivirales/análisis , Antígenos Virales/análisis , ADN Viral/análisis , Antígenos Nucleares del Virus de Epstein-Barr , Femenino , Técnica del Anticuerpo Fluorescente , Genes Virales , Granuloma Letal de la Línea Media/patología , Herpesvirus Humano 4/genética , Humanos , Inmunoglobulina A/análisis , Inmunoglobulina G/análisis , Linfoma/patología , Masculino , Hibridación de Ácido Nucleico , Fenotipo , Linfocitos TRESUMEN
A 34-year-old woman had a granulomatous ulceration of the nose that responded to radiation therapy. The limitation of the disease to the nose and the histologic findings were consistent with a diagnosis of midline granuloma, Stewart type. The relationship of midline granuloma to Wegener's granulomatosis is reviewed. In view of the uniform mortality that accompanies untreated midline granuloma, a correct diagnosis must be made so that radiation therapy can be promptly instituted.