RESUMEN
Soft tissue tumors are uncommon manifestations of Epstein-Barr virus (EBV) infection in patients who have had transplants. The authors report 2 metachronous EBV-containing smooth muscle tumors in a child who had a heart transplant, and review the literature on posttransplant soft tissue tumors.
Asunto(s)
Neoplasias Encefálicas/patología , Infecciones por Virus de Epstein-Barr/diagnóstico , Trasplante de Corazón/efectos adversos , Leiomioma/patología , Neumonía Viral/diagnóstico , Biopsia con Aguja , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/virología , Niño , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Estudios de Seguimiento , Trasplante de Corazón/métodos , Humanos , Inmunohistoquímica , Hibridación in Situ , Leiomioma/complicaciones , Leiomioma/cirugía , Leiomioma/virología , Músculo Liso , Neumonía Viral/complicaciones , Neumonía Viral/cirugíaRESUMEN
Epstein-Barr virus (EBV)-driven post-transplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality following transplantation, and it occurs more frequently in children than in adults. Of 22 (5%) children at our institution who developed tissue-proven PTLD 1-60 months (mean 16.5 months) following organ transplant, 11 died: nine of these 22 patients developed PTLD between 1989 and 1993, and seven (78%) died; the remaining 13 developed PTLD between 1994 and 1998, and four (31%) died (p = 0.08). All nine patients who developed PTLD < 6 months after transplant died, but 11 of 13 patients who manifested disease > or = 6 months after transplant survived (p = 0.0002). Ten of 11 (91%) survivors, but only two of eight (25%) children who died, had serologic evidence of EBV infection at the time of PTLD diagnosis (p = 0.04). EBV seroconversion identified patients at risk for developing PTLD, but also characterized patients with sufficient immune function to survive EBV-related lymphoid proliferation. In situ hybridization for EBER1 mRNA was diagnostically helpful because it detected EBV in tissue sections of all 20 patients with B-cell PTLD, including those with negative serology.
Asunto(s)
Huésped Inmunocomprometido , Trastornos Linfoproliferativos/etiología , Inmunología del Trasplante , Adolescente , Niño , Preescolar , Femenino , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Incidencia , Lactante , Modelos Logísticos , Trastornos Linfoproliferativos/mortalidad , Trastornos Linfoproliferativos/virología , Masculino , ARN Viral/sangre , Resultado del TratamientoRESUMEN
OBJECTIVES: Posttransplant lymphoproliferative disorder (PTLD) causes significant morbidity and mortality, is related to Epstein-Barr virus (EBV) infection, and is more common in children than in adults. We reviewed autopsies of children who died with PTLD to compare postmortem with antemortem PTLD histology, to assess the extent of PTLD, to document associated pathology, and to identify cause of death. METHODS: Postmortem examinations were performed on 7 patients after bone marrow (n = 3) or liver (n = 4) transplant. PTLD was classified histologically as hyperplasia or lymphoma. In situ hybridization for EBER1 messenger RNA was performed on tissue samples from all cases. EBV serologies were used to categorize infections as negative, primary, or reactive. RESULTS: PTLD was diagnosed in 5 children 12 to 35 (mean: 22) days before death, and 1.5 to 4 (mean: 3) months after transplant; PTLD was diagnosed in 2 cases at autopsy 2.5 and 4 months after transplant. Postmortem PTLD histology resembled antemortem histology; 5 PTLDs were lymphoma, 1 was hyperplasia, and 1 contained both lymphoma and hyperplasia. EBER1 messenger RNA was detected in 6 B-cell PTLDs, including lesions from patients who did not have EBV serology that indicated active infection. Complete autopsy of 4 patients who died with biopsy-proven PTLD revealed widely disseminated disease, and lymph node, brain, gastrointestinal tract, and kidney were involved in all 4 patients. Cases diagnosed at autopsy were 1 widely disseminated PTLD that had been suspected but not proven antemortem, and 1 PTLD confined to abdominal lymph nodes that was not suspected antemortem. Severe organ dysfunction (renal failure, gastrointestinal hemorrhage) was caused by massive PTLD infiltration in 2 patients. The conditions other than PTLD that contributed to morbidity and death were organ infection (5 cases), infarcts (4 cases), and diffuse alveolar damage (3 cases). CONCLUSIONS: PTLD may occur within weeks after transplant in children. The distribution of PTLD comprises a spectrum from localized and subclinical to widely disseminated and symptomatic. PTLD may cause demise quickly after the onset of signs and symptoms, through massive organ infiltration or associated conditions, such as diffuse alveolar damage. EBV serology may not accurately reflect the presence or extent of PTLD. Autopsy studies of transplant patients are necessary to identify the true incidence, natural history, and response to treatment of PTLD.
Asunto(s)
Trastornos Linfoproliferativos/patología , Trasplante de Órganos/patología , Complicaciones Posoperatorias/patología , Autopsia , Causas de Muerte , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Lactante , Trasplante de Hígado/patología , Linfoma/patología , Trastornos Linfoproliferativos/diagnóstico , Masculino , Complicaciones Posoperatorias/diagnósticoRESUMEN
Hepatosplenic gammadelta T-cell lymphoma is a distinct entity, characterized by occurrence in young adult males with hepatosplenomegaly, B-symptoms, peripheral blood cytopenias, and no lymphadenopathy; lymphomatous infiltrates in the splenic red pulp, hepatic sinusoids, and bone marrow sinuses; T-cell receptor (TCR) gammadelta chains and a cytotoxic T-cell phenotype; isochromosome 7q; and an aggressive clinical course. In comparison, this study describes the clinicopathologic features of 14 hepatosplenic T-cell lymphomas expressing TCR alphabeta chains. They occurred in 11 women and 3 men with a median age of 36 years. Clinical presentation was similar to that described previously for hepatosplenic gammadelta T-cell lymphomas, except for the female preponderance and age distribution (5 patients younger than 13 years of age and 5 patients older than 50 years of age). Disease distribution was primarily in the splenic red pulp and hepatic sinusoids, although liver infiltrates were largely periportal in four cases. Bone marrow involvement, observed in eight patients, was usually interstitial and/or within the sinuses. Lymph nodes were involved in five patients, although lymphadenopathy was demonstrable in only two. Ten cases were composed of intermediate-size tumor cells with round/oval nuclei, slightly dispersed chromatin, inconspicuous nucleoli, and scant to moderate amounts of cytoplasm. Four lymphomas contained primarily large cells with irregular nuclei, dispersed chromatin, discernible nucleoli, and moderate to abundant cytoplasm. Tumor cells in all 14 lymphomas were cytotoxic alphabeta T-cells; 13 co-expressed natural killer cell-associated antigens and showed T-cell clonality. Three lymphomas were associated with Epstein-Barr virus. Two of four cases had an isochromosome 7q. Eleven patients are dead, eight within a year of diagnosis, and two patients have maintained complete remissions after combination chemotherapy. These data show that hepatosplenic T-cell lymphomas include an alphabeta-subtype. This group, along with the previously recognized gammadelta group, should be recognized as phenotypically heterogeneous subtypes of the same disease entity.
Asunto(s)
Neoplasias Hepáticas/patología , Linfoma de Células T/patología , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Neoplasias del Bazo/patología , Adulto , Anciano , Anciano de 80 o más Años , Médula Ósea/patología , Niño , Preescolar , ADN de Neoplasias/análisis , Femenino , Reordenamiento Génico de la Cadena gamma de los Receptores de Antígenos de los Linfocitos T/genética , Humanos , Lactante , Recién Nacido , Cariotipificación , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Ganglios Linfáticos/patología , Linfoma de Células T/clasificación , Linfoma de Células T/genética , Linfoma de Células T/metabolismo , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Neoplasias del Bazo/genética , Neoplasias del Bazo/metabolismoRESUMEN
We report 2 cases of renal transplant recipients in whom hepatosplenic gamma-delta T-cell lymphoma (gamma-delta HSTCL) developed 5 and 10 years after transplantation. Both patients had marked hepatosplenomegaly, B symptoms (weight loss, fever, and night sweats), and abnormal peripheral blood findings, including anemia in both, thrombocytopenia and leukoerythroblastic changes in 1, and leukocytosis in the other. Markedly atypical lymphoid infiltrate of intermediate to large cells was observed in the spleen, liver, and bone marrow. The malignant cells showed typical immunophenotype of gamma-delta T cells (CD2+, CD3+, CD4-, CD8-, CD7+, gamma-delta T-cell receptor-positive, and alpha-beta T-cell receptor-negative) with clonal T-cell receptor gene rearrangement and were of the V-delta-1 subset. In addition, the cells contained a cytolytic granule-associated protein, TIA-1, and Fas ligand, indicating cytotoxic T-cell differentiation. The malignant T cells in both cases were of host tissue origin. Both cases were negative for Epstein-Barr virus genome using Southern blot analysis. The patients did not respond to reduction of immunosuppression. Despite initial response to chemotherapy, both patients died within 6 months of diagnosis. Our findings indicate that gamma-delta HSTCL can occur as a late complication in transplant recipients.
Asunto(s)
Trasplante de Riñón/efectos adversos , Neoplasias Hepáticas/etiología , Linfoma de Células T/etiología , Proteínas , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Neoplasias del Bazo/etiología , Adulto , ADN de Neoplasias/análisis , Proteína Ligando Fas , Resultado Fatal , Femenino , Reordenamiento Génico de la Cadena delta de los Receptores de Antígenos de los Linfocitos T/genética , Humanos , Inmunofenotipificación , Hibridación Fluorescente in Situ , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Linfoma de Células T/inmunología , Linfoma de Células T/patología , Masculino , Glicoproteínas de Membrana/metabolismo , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Proteínas de Unión a Poli(A) , Reacción en Cadena de la Polimerasa , Proteínas de Unión al ARN/metabolismo , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Receptores de Interleucina-2/sangre , Neoplasias del Bazo/inmunología , Neoplasias del Bazo/patología , Antígeno Intracelular 1 de las Células TRESUMEN
We present the clinical and pathologic findings of a case of sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid in a 39-year-old woman. This particular case is notable because it initially presented as a cervical lymph node metastasis, and the initial clinical and histologic impression was Hodgkin disease, nodular sclerosis type. Sclerosing mucoepidermoid carcinoma with eosinophilia is a differentiated malignant neoplasm of the thyroid that can be confused with anaplastic carcinoma, medullary carcinoma, squamous cell carcinoma, or, as in this case, Hodgkin disease. A correct diagnosis of sclerosing mucoepidermoid carcinoma with eosinophilia involves awareness of this entity and appropriate immunohistochemical analysis. In this article, we briefly review the literature and stress the histologic and cytologic findings characteristic of sclerosing mucoepidermoid with eosinophilia of the thyroid.
Asunto(s)
Carcinoma Mucoepidermoide/complicaciones , Eosinofilia/complicaciones , Ganglios Linfáticos/patología , Neoplasias de la Tiroides/complicaciones , Adulto , Biomarcadores de Tumor/análisis , Biopsia con Aguja , Carcinoma Mucoepidermoide/química , Carcinoma Mucoepidermoide/diagnóstico , Carcinoma Mucoepidermoide/cirugía , Diagnóstico Diferencial , Eosinofilia/diagnóstico , Femenino , Enfermedad de Hodgkin/diagnóstico , Humanos , Inmunohistoquímica , Ganglios Linfáticos/cirugía , Metástasis Linfática , Cuello/patología , Disección del Cuello , Neoplasias de la Tiroides/química , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/cirugía , Tomografía Computarizada por Rayos XRESUMEN
Tumor-infiltrating lymphocytes (TIL) have been shown to be an independent prognostic factor in melanomas. To better characterize the host immune response, we have classified TIL by their immunoreactivity against lymphoid markers in formalin-fixed, paraffin-embedded tissue. Monoclonal antibodies to leukocyte common antigen (LCA) and TIA-1 (a granule-associated protein of cytotoxic T cells and NK cells) were used to immunostain a series of benign nevi, nontumorigenic radial growth phase, and tumorigenic vertical growth phase melanomas and metastases. Among nine nevi, few LCA+ TIL were found, among which rare cells were positive for TIA-1 (mean, 2.0). Five nontumorigenic radial growth phase melanomas also had few total TIL and rare TIA-1+ TIL (mean, 3.4); the nontumorigenic radial growth phase component of seven tumorigenic vertical growth phase melanomas had higher numbers of TIA-1+ TIL (mean, 11). Twelve cases of tumorigenic vertical growth phase melanoma showed a variable but significantly greater number of both LCA+ TIL and TIA-1+ TIL (mean, 30.6). Nine cases of metastatic melanoma had a wide range of variation in LCA as well as in TIA-1+ TIL (mean, 46). Although the mean total number of TIA-1+ TIL increased from nontumorigenic radial growth phase to tumorigenic vertical growth phase to metastases, TIA-1+ as a percentage of TIL declined across these categories of tumor progression (42%, 31%, and 26%, respectively). Our results show that these attributes of TIA-1+ TIL, both increasing total number but decreasing percentage, appear to be a marker of tumor progression of malignant melanomas. In addition, there was significant variability in the number of TIA-1+ TIL among advanced melanomas, raising the possibility that an assessment of TIA-1+ TIL may prove a useful prognostic tool for the evaluation of primary melanomas.
Asunto(s)
Células Asesinas Naturales/patología , Linfocitos Infiltrantes de Tumor/patología , Melanoma/patología , Proteínas de la Membrana/análisis , Nevo/patología , Proteínas , Proteínas de Unión al ARN/análisis , Neoplasias Cutáneas/patología , Linfocitos T Citotóxicos/patología , Humanos , Técnicas para Inmunoenzimas , Células Asesinas Naturales/química , Antígenos Comunes de Leucocito/análisis , Linfocitos Infiltrantes de Tumor/química , Melanoma/química , Melanoma/inmunología , Nevo/química , Nevo/inmunología , Proteínas de Unión a Poli(A) , Pronóstico , Neoplasias Cutáneas/química , Neoplasias Cutáneas/inmunología , Antígeno Intracelular 1 de las Células T , Linfocitos T Citotóxicos/químicaRESUMEN
Gamma/delta T cell lymphomas (gamma/delta TCL) represent rare, often aggressive types of T cell malignancy that are clinically and pathologically diverse. Most gamma/delta TCL occur as a hepatosplenic or subcutaneous type. To date, analysis of the T cell receptor delta (TCRS) gene repertoire of hepatosplenic gamma/delta TCL (gamma/delta HSTCL) and subcutaneous panniculitis-like gamma/delta TCL (gamma/delta SPTCL) has been reported only in a limited number of cases. In this study we analyzed 11 gamma/delta HSTCL and 4 gamma/delta SPTCL by polymerase chain reaction and immunostaining to determine their usage of the Vdelta subtypes (Vdelta1-6). It is noteworthy that 10 of 11 gamma/delta HSTCL expressed the Vdelta1 gene. The remaining case also expressed T cell receptor delta (TCRS) as determined by flow cytometry and TCRdelta rearrangement in Southern blot. However, the Vdelta gene expressed by this lymphoma could not be determined, which suggests usage of an as yet unidentified Vdelta gene. In striking contrast to the gamma/delta HSTCL, all 4 gamma/delta SPTCL expressed the Vdelta2 gene. Our data demonstrate that gamma/delta HSTCL are preferentially derived from the Vdelta1 subset of gamma/delta T lymphocytes, whereas gamma/delta SPTCL are preferentially derived from the Vdelta2 subset. The pattern of Vdelta gene expression in HSTCL and SPTCL corresponds to the respective, predominant gamma/delta T cell subsets normally found in the spleen and skin. This finding suggests that gamma/delta TCL are derived from normal gamma/delta T lymphocytes which reside in the affected tissues. Furthermore, the selective, lymphoma type-specific Vdelta gene segment usage may provide a molecular tool to distinguish better among various types of gamma/delta TCL lymphoma particularly in the clinically advanced, widely disseminated cases.
Asunto(s)
Linfoma de Células T/genética , Linfoma de Células T/inmunología , Paniculitis/genética , Paniculitis/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Subgrupos de Linfocitos T/inmunología , Adolescente , Adulto , Anciano , Secuencia de Bases , Cartilla de ADN/genética , Femenino , Reordenamiento Génico de la Cadena delta de los Receptores de Antígenos de los Linfocitos T , Reordenamiento Génico de la Cadena gamma de los Receptores de Antígenos de los Linfocitos T , Humanos , Hibridación Fluorescente in Situ , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patología , Linfoma de Células T/patología , Masculino , Persona de Mediana Edad , Paniculitis/patología , Reacción en Cadena de la Polimerasa , Neoplasias del Bazo/genética , Neoplasias del Bazo/inmunología , Neoplasias del Bazo/patología , Subgrupos de Linfocitos T/patologíaRESUMEN
Acute promyelocytic leukemia (APL) represents a subtype of acute myeloid leukemia with characteristic morphologic, molecular, and immunophenotypic features. Previous immunophenotypic analyses have shown that leukemic cells in APL typically express the myeloid markers CD33 and CD13 but lack expression of the early hematopoietic progenitor cell antigens CD34 and HLA-DR. We analyzed selected immunophenotypic features of APL by flow cytometry and showed that 7 (41%) of 17 cases contained significant subsets of CD34+ leukemic cells: CD34+ myeloid cells predominated in 2 APL cases. By using a fluorescence-activated cell sorter-fluorescence in situ hybridization approach, we confirmed that the CD34+ cells harbored the t(15;17) translocation characteristic of APL. By using the same experimental approach, CD34+ populations were stratified into primitive CD34+ CD38- and committed CD34+ CD38+ progenitor cell subpopulations; cells in both subsets contained the t(15;17) translocation. The knowledge that APL may be partly or largely CD34+ is important for proper diagnosis. Furthermore, identification of the t(15;17) translocation in CD34+ CD38- blasts indicates that, in at least some cases, the leukemogenic mutation in APL occurs within primitive hematopoietic progenitor cells.
Asunto(s)
Células Madre Hematopoyéticas/inmunología , Leucemia Promielocítica Aguda/genética , Antígenos CD34/análisis , Antineoplásicos/uso terapéutico , Cromosomas Humanos Par 15 , Cromosomas Humanos Par 17 , Citometría de Flujo , Antígenos HLA-DR/análisis , Células Madre Hematopoyéticas/patología , Humanos , Inmunofenotipificación , Cariotipificación , Leucemia Promielocítica Aguda/tratamiento farmacológico , Leucemia Promielocítica Aguda/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Translocación Genética , Tretinoina/uso terapéuticoRESUMEN
The intent of this article is to describe the effect of tumor lysis on automated platelet counts in therapy-related, secondary acute monocytic leukemia. The first patient was a 69-year-old man with large cell carcinoma of the lung who developed acute monocytic leukemia 1(1/2) years after initiation of radiation and chemotherapy for his carcinoma. The second patient was a 72-year-old female with peripheral T-cell lymphoma who developed acute monocytic leukemia 1 year after initiation of chemotherapy for her lymphoma. Platelet counts were determined by the automated Coulter (STKS) counter. Both patients had clinical and laboratory evidences of tumor lysis syndrome and disseminated intravascular coagulation. The peripheral blood smears revealed numerous fragments of leukemic cells and apoptotic cells with pyknotic nuclei. The Coulter machine enumerated these cellular fragments as platelets, resulting in falsely elevated platelet counts. Awareness of this laboratory artifact in secondary acute monocytic leukemia with tumor lysis syndrome is important so that potential life-threatening thrombocytopenia is not overlooked.
Asunto(s)
Leucemia Monocítica Aguda/sangre , Neoplasias Primarias Secundarias/sangre , Recuento de Plaquetas , Síndrome de Lisis Tumoral/sangre , Anciano , Carcinoma de Células Grandes/complicaciones , Coagulación Intravascular Diseminada/sangre , Coagulación Intravascular Diseminada/complicaciones , Coagulación Intravascular Diseminada/diagnóstico , Reacciones Falso Negativas , Femenino , Humanos , Leucemia Monocítica Aguda/complicaciones , Neoplasias Pulmonares/complicaciones , Linfoma de Células T/complicaciones , Masculino , Neoplasias Primarias Secundarias/complicaciones , Trombocitopenia/sangre , Trombocitopenia/complicaciones , Trombocitopenia/diagnóstico , Síndrome de Lisis Tumoral/complicaciones , Síndrome de Lisis Tumoral/diagnósticoRESUMEN
The use of ancillary techniques to aid in the diagnosis of metastatic carcinoma in serous effusions has been the subject of numerous studies. In this article, we study 35 cases of malignant effusions (metastatic adenocarcinoma) and 20 benign effusions using a panel of immunohistochemical markers to determine whether changes in the subpopulations of accompanying lymphoid cells can be detected with this technique and whether such changes are associated with the presence of malignancy. We noted a significant increase in cytotoxic lymphocytes, defined as the percentage of all lymphoid cells staining with an antibody to TIA-1 (an antigen localized to the cytotoxic granule membranes of cytotoxic T cells and natural killer cells) in malignant compared with benign effusions (23% vs. 12%; P < 0.05). In addition, nearly all cases in which cytotoxic lymphocytes composed > 20% of the lymphoid cell population contained metastatic tumor. Thus, immunohistochemical staining for TIA-1 can reliably detect cytotoxic lymphocytes in cell blocks of serous effusions; in addition, a relative increase in their number is associated with the presence of malignancy.
Asunto(s)
Inmunohistoquímica , Derrame Pleural Maligno/inmunología , Proteínas , Linfocitos T Citotóxicos , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/análisis , Líquido Ascítico/citología , Complejo CD3/análisis , Antígenos CD79 , Femenino , Humanos , Leucosialina , Masculino , Proteínas de la Membrana/análisis , Persona de Mediana Edad , Derrame Pericárdico/citología , Derrame Pericárdico/inmunología , Derrame Pleural Maligno/citología , Proteínas de Unión a Poli(A) , Proteínas de Unión al ARN/análisis , Receptores de Antígenos de Linfocitos B/análisis , Sialoglicoproteínas/análisis , Antígeno Intracelular 1 de las Células T , Linfocitos T Citotóxicos/inmunologíaRESUMEN
BACKGROUND: Follicular lymphoma in childhood is rare. The authors present four unusual primary follicular lymphomas of the testis in children. METHODS: Tumor tissue was evaluated using light microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction (PCR) for immunoglobulin heavy chain (IgH) and bcl-2 gene rearrangements. Southern blot and immunohistochemical analyses were used to detect bcl-6 gene rearrangements and protein expression, respectively. RESULTS: Four young boys ranging in age from 3 to 10 years were diagnosed with Stage IE follicular large cell lymphoma (Grade 3). A B-cell phenotype was documented in all four cases; monoclonality was confirmed in three cases by demonstration of light chain restriction or clonal IgH gene rearrangement. None of the lymphomas expressed Bcl-2 or p53 protein, and bcl-2 gene rearrangements were not found in the three lymphomas studied. In contrast, Bcl-6 protein was expressed by all three lymphomas studied, and a bcl-6 gene rearrangement was detected in the one case analyzed by Southern blot. All four boys were treated by orchiectomy and combination chemotherapy and are alive with no evidence of disease 18-44 months following their initial diagnoses. CONCLUSIONS: Follicular lymphomas may rarely occur as primary testicular tumors in prepubertal boys and, when localized, appear to be associated with a favorable prognosis. In contrast to follicular lymphoma in adults, pediatric follicular lymphomas of the testis are usually of large cell type (Grade 3) and lack bcl-2 or p53 abnormalities. The identification, in one case, of a bcl-6 gene rearrangement suggests an alternate molecular pathogenesis for pediatric follicular lymphoma.
Asunto(s)
Linfoma Folicular/genética , Neoplasias Testiculares/genética , Niño , Preescolar , Reordenamiento Génico , Humanos , Inmunofenotipificación , Linfoma de Células B/genética , Linfoma Folicular/patología , Masculino , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Neoplasias Testiculares/patología , Proteína p53 Supresora de Tumor/análisisRESUMEN
A 39-yr-old man with stage IV Hodgkin's disease (HD) involving bone marrow was being evaluated for autologous bone marrow transplantation when he developed diplopia, prompting a lumbar puncture tap for cerebral spinal fluid (CSF) examination. Cytologic examination of the CSF revealed numerous Reed-Sternberg (RS) cells in a polymorphous inflammatory background of small lymphocytes, monocytes, rare plasma cells, and eosinophils. However, magnetic resonance imaging (MRI) studies of the brain and spinal cord failed to reveal evidence of leptomeningeal disease or intracranial masses. Repeat CSF examination again demonstrated cytologic evidence of HD. Immunocytochemical stains established that the RS cells and mononuclear Hodgkin's cells were positive for CD30 and CD20 but negative for CD15; this phenotype was identical to that of RS cells in the initial diagnostic bone marrow biopsy, confirming CSF involvement by HD. The patient was treated with intrathecal methotrexate, 15 mg, 6 days after his bone marrow transplant. After treatment, all subsequent CSF cytology specimens were negative for tumor. In this case of disseminated HD, cytologic examination allowed for early detection of CNS involvement by lymphoma prior to development of radiographically detectable lesions.
Asunto(s)
Líquido Cefalorraquídeo/citología , Enfermedad de Hodgkin/diagnóstico , Inmunohistoquímica , Adulto , Biopsia , Células de la Médula Ósea/patología , Líquido Cefalorraquídeo/química , Humanos , Masculino , Reacción en Cadena de la PolimerasaRESUMEN
Anaplastic large cell lymphomas (ALCL) are a heterogeneous group of CD30+ large cell lymphomas; the most characteristic type have a T or null cell phenotype, often express epithelial membrane antigen (EMA) and cytolytic lymphocyte markers, and often possess a nonrandom t(2;5)(p23;q35) chromosomal translocation. We studied 22 (19 T, 1 null, 2 B cell) ALCL, including four primary cutaneous ALCL (PC-ALCL), for the expression of TIA-1, the cytotoxic T lymphocyte (CTL) or natural killer (NK) cell-associated antigens CD4, CD8, betaF1, TCRdelta1, CD56, and CD57, the ALCL-associated antigens p80 and EMA, and the Hodgkin's disease-associated marker CD15 to better define the relationship of these markers to histological subtype, primary site, and patient clinical characteristics. TIA-1 expression was seen in 12 of 20 (60%) T or null cell ALCLs with a cytoplasmic, granular distribution. Ultrastructural studies showed cytotoxic-type granules (dense core, multivesicular, and intermediate types) with TIA-1 localized to granules on immunogold labeling. TIA-1 staining strongly correlated with young patient age (< or = 32 years, P < .05) and EMA expression (P < .05). Excluding the four PC-ALCL cases, TIA-1 staining also correlated with p80 expression (P < .05) in all of the T cell cases. Three CD15+ cases were TIA-1-. TIA-1 expression in T or null cell ALCL was seen in all morphological subtypes (2 of 2 small cell variant, 3 of 4 monomorphic variant, and 7 of 14 pleomorphic variant) and primary tumor sites (6 of 14 nodal, 2 of 4 primary cutaneous, 2 of 2 bone, and 2 of 2 soft tissue). TIA-1+ granules were seen in all subsets: 5 of 6 CD4+, 1 of 2 CD8+, 4 of 8 CD56+, and 1 of 2 CD57+ ALCL. Of note, 4 of 10 T or null cell ALCL expressed gammadelta T-cell receptors (TCR), whereas only 1 of 10 T or null cell ALCL was alphabeta TCR+; TCR were not detected in five cases. TIA-1 was expressed by 3 of 4 gammadelta TCR+ ALCL and 1 of 1 alphabeta TCR+ ALCL. These data support a cytotoxic lymphocyte phenotype in most T or null cell ALCL and suggest that some T cell ALCL are derived from cytolytic CD4+ T cells, gammadelta T cells, or NK-like (CD56+ or CD57+) T cells.
Asunto(s)
Antígenos CD/biosíntesis , Linfoma Anaplásico de Células Grandes/metabolismo , Proteínas de la Membrana/biosíntesis , Proteínas , Proteínas de Unión al ARN/biosíntesis , Receptores de Antígenos de Linfocitos T/biosíntesis , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Inmunofenotipificación , Lactante , Linfoma Anaplásico de Células Grandes/patología , Linfoma Anaplásico de Células Grandes/ultraestructura , Masculino , Microscopía Inmunoelectrónica , Persona de Mediana Edad , Mucina-1/biosíntesis , Proteínas de Fusión Oncogénica/biosíntesis , Proteínas de Unión a Poli(A) , Proteínas Tirosina Quinasas/biosíntesis , Antígeno Intracelular 1 de las Células TRESUMEN
Immunophenotyping by flow cytometry is widely used in the diagnosis and subclassification of acute myeloid leukemia (AML). CD14 is the monocyte-associated antigen most widely used to identify AML with monocytic differentiation (French-American-British classes M4 and M5); however, we observed that CD14 expression is frequently diminished or absent in such cases. To identify monocyte-associated antigens that might improve recognition of AML M4 and M5, we used 3-color flow cytometry and a panel of antibodies reported to distinguish cells of monocytic lineage in 44 cases of AML. In addition, CD45 vs logarithmic side scatter plots were analyzed in all cases. As expected, CD14 was highly specific but was only moderately sensitive for monocytic differentiation. CD64 had the best-combined sensitivity and specificity for AML M4 and M5. CD45 vs logarithmic side scatter analysis showed a higher percentage of monocytes in AML M4 and M5 compared with nonmonocytic AML. CD64 was expressed in 5 of 5 cases of acute promyelocytic leukemia (AML M3), but the intensity of staining was significantly less in AML M3 than in AML M4 and M5. Our findings show that addition of CD64 and CD45 vs logarithmic side scatter analysis to CD14 greatly improves flow cytometric detection of AML with monocytic differentiation and that CD64, also expressed in AML M3, may help distinguish AML M3 from other subtypes.
Asunto(s)
Leucemia Mieloide Aguda/clasificación , Leucemia Mieloide Aguda/patología , Antígenos Comunes de Leucocito/análisis , Receptores de IgG/análisis , Citometría de Flujo , Humanos , Inmunofenotipificación , Leucemia Mieloide Aguda/sangre , Sensibilidad y EspecificidadRESUMEN
Expression of a dominant negative mutant IFNgammaR1 in murine SCK and K1735 tumor cells rendered them relatively unresponsive to IFNgamma in vitro and more tumorigenic and less responsive to IL-12 therapy in vivo. IL-12 induced histologic evidence of ischemic damage only in IFNgamma-responsive tumors, and in vivo Matrigel vascularization assays revealed that while IFNgamma-responsive and -unresponsive tumor cells induced angiogenesis equally well, IL-12 and its downstream mediator IFNgamma only inhibited angiogenesis induced by the responsive cells. IL-12 induced angiogenesis inhibitory activity in the responsive cells, which may be attributable to production of the chemokine IP-10. Thus, IL-12 and IFNgamma inhibit tumor growth by inducing tumor cells to generate antiangiogenic activity.
Asunto(s)
Antineoplásicos/uso terapéutico , Interferón gamma/farmacología , Interleucina-12/uso terapéutico , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Melanoma Experimental/tratamiento farmacológico , Neovascularización Patológica , Animales , Femenino , Expresión Génica , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Endogámicos A , Ratones Endogámicos C3H , Mutagénesis , Receptores de Interferón/genética , Receptores de Interferón/metabolismo , Proteínas Recombinantes , Células Tumorales Cultivadas , Receptor de Interferón gammaRESUMEN
Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an uncommon cutaneous lymphoma that has been proposed as a distinct clinicopathologic entity, but studies of SPTCL are limited. We studied the clinicopathologic, immunophenotypic, and genetic features of 11 SPTCLs. All cases had a variable admixture of pleomorphic small, medium, or large lymphocytes and histiocytes infiltrating the subcutis in a lobular panniculitis-like pattern. A granulomatous reaction was seen in three cases and erythrophagocytosis in four. Karyorrhexis and fat necrosis were present in all cases. Angioinvasion was seen in seven SPTCLs; four had areas of coagulation necrosis. All cases expressed T-cell-associated antigens (CD3epsilon, CD45RO, or CD43) and T-cell receptors (TCR); nine expressed alphabeta TCRs and two expressed gammadelta TCRs. T-cell receptor-gamma, TCRbeta, or TCRdelta genes were clonally rearranged in 8 of 10 cases studied. Both gammadelta SPTCLs expressed Vdelta2+ TCRs and were CD4-, CD8- and CD56+. CD56 was negative in seven of nine alphabeta SPTCLs and inconclusive in the other two. Six of nine alphabeta SPTCLs were CD8+; the CD4/CD8 phenotypes were indeterminate in the other three. Cytolytic granule-associated proteins were expressed by all SPTCLs (11 of 11 were TIA-1+, 4 of 4 were perforin+). In situ hybridization for Epstein-Barr virus-encoded RNA (EBER-1) was negative in all cases. Most patients responded to systemic chemotherapy or local radiation therapy. Seven patients are alive: four without disease (19-73 months) and three with disease (32-72 months); four died: three of disease (3-25 months) and one without disease (42 months). We conclude that SPTCLs are clonal, EBV-, cytotoxic T-cell lymphomas derived from alphabeta T-cells or gammadelta T-cells. The gammadelta SPTCLs appear to be preferentially derived from the Vdelta2+ subset. Subcutaneous panniculitis-like T-cell lymphoma may be rapidly fatal or indolent; local therapy may be appropriate for some patients.
Asunto(s)
Linfoma Cutáneo de Células T , Paniculitis/patología , Receptores de Antígenos de Linfocitos T alfa-beta/análisis , Receptores de Antígenos de Linfocitos T gamma-delta/análisis , Neoplasias Cutáneas , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/análisis , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , ADN de Neoplasias/análisis , Femenino , Reordenamiento Génico de Linfocito T/genética , Genotipo , Herpesvirus Humano 4/genética , Humanos , Técnicas para Inmunoenzimas , Inmunofenotipificación , Hibridación in Situ , Linfoma Cutáneo de Células T/química , Linfoma Cutáneo de Células T/genética , Linfoma Cutáneo de Células T/inmunología , Linfoma Cutáneo de Células T/patología , Masculino , Persona de Mediana Edad , Paniculitis/genética , Paniculitis/inmunología , ARN Viral/análisis , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Neoplasias Cutáneas/química , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patologíaRESUMEN
PURPOSE: To determine the radiographic findings of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma on double-contrast upper gastrointestinal studies. MATERIALS AND METHODS: Pathology records, double-contrast upper gastrointestinal studies, and medical records of six patients with gastric MALT lymphoma were retrospectively reviewed. RESULTS: The most common clinical findings at presentation included epigastric pain (n = 6), dyspepsia (n = 4), and nausea and vomiting (n = 4). Double-contrast studies revealed rounded, often confluent nodules of varying size in four patients with low-grade MALT lymphoma. Nodularity was located in the gastric antrum (n = 2), body (n = 1), or body and fundus (n = 1). A fifth patient had a malignant-appearing 1-cm-diameter antral ulcer, and a sixth had a 10-cm-diameter polypoid, ulcerated mass in the gastric fundus. The latter patient was found to have high-grade MALT lymphoma with low-grade MALT lymphoma abutting the tumor. Five patients had associated Helicobacter pylori gastritis. Five patients had stage I disease, and one had stage IIB disease. At endoscopic follow-up (n = 4), marked regression of tumor occurred after treatment with antibiotics, chemotherapy, and/or radiation therapy. CONCLUSION: When low-grade MALT lymphoma is suspected on the basis of barium study results, endoscopic biopsy specimens should be obtained for a definitive diagnosis so these patients can be treated before the development of high-grade gastric lymphoma.
Asunto(s)
Mucosa Gástrica/diagnóstico por imagen , Linfoma de Células B de la Zona Marginal/diagnóstico por imagen , Neoplasias Gástricas/diagnóstico por imagen , Anciano , Antibióticos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Medios de Contraste/administración & dosificación , Dispepsia/fisiopatología , Femenino , Estudios de Seguimiento , Fundus Gástrico/diagnóstico por imagen , Mucosa Gástrica/patología , Gastritis/microbiología , Gastritis/patología , Gastroscopía , Infecciones por Helicobacter/patología , Helicobacter pylori , Humanos , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/patología , Linfoma de Células B de la Zona Marginal/radioterapia , Masculino , Persona de Mediana Edad , Náusea/fisiopatología , Estadificación de Neoplasias , Dolor/fisiopatología , Pólipos/diagnóstico por imagen , Pólipos/patología , Antro Pilórico/diagnóstico por imagen , Radiografía , Inducción de Remisión , Estudios Retrospectivos , Estómago/diagnóstico por imagen , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/radioterapia , Úlcera Gástrica/diagnóstico por imagen , Úlcera Gástrica/patología , Vómitos/fisiopatologíaRESUMEN
Hodgkin's disease rarely presents as obstructive jaundice. We report a case of Hodgkin's disease arising in periduodenallymph nodes, presenting with biliary obstruction, definitively diagnosed on cytologic material obtained by endosonographically-guided real-time fine needle aspiration biopsy and confirmed at laparotomy. The medical literature pertaining to the use of endosonography and fine needle aspiration biopsy for pancreatic lesions and abdominal lymphoma is reviewed. Currently available data support the use of fine needle aspiration biopsy in establishing the diagnosis of lymphoma. This case highlights the utility of endoscopic ultrasonography with endosonographically guided real-time fine needle aspiration biopsy in diagnosing and managing patients with extrahepatic biliary obstruction or suspected abdominal lymphoma. Pairing endosonographically guided real-time fine needle aspiration biopsy with on-site cytologic assessment and immediate specimen triage can lead to definitive diagnosis of abdominal lymphoma, avoiding surgical intervention in many cases.
Asunto(s)
Biopsia con Aguja , Endosonografía , Enfermedad de Hodgkin/diagnóstico , Ganglios Linfáticos/patología , Ultrasonografía Intervencional , Adulto , Colestasis Extrahepática/etiología , Duodeno , Enfermedad de Hodgkin/complicaciones , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/patología , Humanos , MasculinoRESUMEN
Peripheral T-cell lymphomas (PTCLs) are often diagnosed after demonstration of T-lineage-related antigen expression on neoplastic lymphocytes by paraffin immunoperoxidase (PIP). However, complete T-cell subset analysis for helper, suppressor/cytotoxic, alphabeta, and gammadelta phenotypes has not been examined by PIP. Therefore, PIP was performed for CD4, CD8, T-cell intracellular antigen (TIA)-1, and betaF1 expression in 31 PTCLs previously studied for CD4 and CD8 by flow cytometry. The CD4 and CD8 results from both methods were compared. All betaF1- PTCLs were studied for T-cell receptor (TCR)gammadelta by PIP. PIP showed 71% correlation with the 21 PTCLs that had distinct CD4+ CD8- or CD4- CD8+ phenotypes by flow cytometry, with 64% and 90% sensitivity for CD4 and CD8 expression, respectively. Tumor cells in four of six PTCLs that had no clear CD4 or CD8 predominance or coexpression of these antigens by flow cytometry were shown to be CD4+ CD8- or CD4- CD8+ by PIP. Twelve (39%) PTCLs demonstrated a cytotoxic (TIA-1+) phenotype by PIP, including eight CD4- CD8+, one CD4+ CD8- and three CD4- CD8- cases. Of 30 immunoreactive PTCLs, 26 (87%) were alphabeta (betaF1+) by PIP. Both large cell cases among four betaF1- PTCLs were TCRgammadelta+ by PIP, including one gammadelta+ case confirmed by flow cytometry. We conclude that CD4 and CD8 T-cell subsets can be assigned for most PTCLs by PIP, with CD4 showing moderate and CD8 showing strong correlation with flow cytometric results. PIP can also define CD4 or CD8 expression on tumor cells in the PTCLs in which flow cytometry produces inconclusive results. Cytotoxic PTCLs can be identified easily with TIA-1, which can also distinguish cytotoxic from "suppressor" CD8+ PTCLs. Most PTCLs are derived from alphabeta T-cells, however some large cell gammadelta PTCLs may be identified by PIP.