Cytomegalovirus Pneumonia after Anti-CC-chemokine Receptor 4 Monoclonal Antibody (Mogamulizumab) Therapy in an Angioimmunoblastic T-cell Lymphoma Patient.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive T-cell lymphoma. A 63-year-old man was diagnosed with AITL. He received 6 cycles of CHOP therapy, but showed progressive disease. Subsequently, he received ESHAP chemotherapy; however, it was not effective. He received mogamulizumab (an anti-CCR4 monoclonal antibody). After 4 cycles, his respiratory condition worsened and he was diagnosed with cytomegalovirus (CMV) pneumonia. Despite antiviral and antibiotic therapy, he died. We speculate that the combination of progressive lymphoma with mogamulizumab and chemotherapy likely caused CMV pneumonia. Because mogamulizumab therapy causes immunosuppression, if CMV pneumonia is suspected, then rapid treatment should be initiated.

Angioimmunoblastic T-cell lymphoma of cytotoxic T-cell phenotype containing a large B-cell proliferation with an undersized B-cell clonal product.

Angioimmunoblastic T-cell lymphoma is a nodal peripheral T-cell lymphoma considered to be derived from CD4 follicular helper T cells. It is characterized by the proliferation of arborizing vessels, hyperplastic follicular dendritic cells, and a polymorphous lymphoid infiltrate including large B immunoblasts, which could be polyclonal, oligoclonal, or monoclonal. The polymerase chain reaction-based clonality study of lymphoproliferations is increasingly popular in the diagnostic workup. With the commercially available Biomed-2 protocols, lymphoproliferations with amplicons in the expected size ranges are considered clonal, whereas clonal products outside the expected ranges are extremely rare. We presented the case of a 60-year-old male patient with angioimmunoblastic T-cell lymphoma, in which the neoplastic T cells expressed CD8, bcl-6, and programmed death-1. Furthermore, there was a proliferation of large B cells in this tumor. The results of T-cell receptor gene rearrangement study using the Biomed-2 protocols showed clonal rearrangement with amplicons falling within the expected size ranges. Interestingly, the size of the amplicons detected by the Biomed-2 immunoglobulin heavy chain gene (IgH) rearrangement using FR2/JH primers was around 240 bp, slightly smaller than the expected size ranges. Through cloning, sequencing, and BLAST searches, we confirmed that the FR2/JH amplicon was derived from the IgH rearrangement with a deletion of a short segment. Our case illustrates that polymerase chain reaction amplicons outside the expected size ranges may still be clonal products.

Evaluation and management of angioimmunoblastic T-cell lymphoma: a review of current approaches and future strategies.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare and complex lymphoproliferative disorder, clinically characterized by widespread lymphadenopathy, extranodal disease, immune-mediated hemolysis, and polyclonal hypergammaglobulinemia. Significant progress has been made in the understanding of AITL since its recognition as a clonal T-cell disorder with associated deregulation of B-cells and endothelial cells within a unique malignant microenvironment. However, as the responses to conventional chemotherapy have not been durable, prognosis with current treatment approaches has remained dismal. Here we review the clinical presentation, prognosis, and management of patients with AITL. We discuss recent developments in the understanding of the pathogenesis of AITL at a cellular and molecular level, including the implication of the follicular helper T-cell as the corresponding cell of origin, the roles of Epstein-Barr virus, B-cell deregulation, angiogenesis, and other signaling pathways in AITL, and the therapeutic implications of these findings. Finally, we discuss recent clinical trials and novel treatment approaches in the management of patients with AITL.

Sustained remission from angioimmunoblastic T-cell lymphoma induced by alemtuzumab.

BACKGROUND: A 73-year-old woman presented with acute lower back pain, fever, chills and arthralgias. She had previously had a positive protein derivative test with a negative chest X-ray; her medical history was also remarkable for a mitral valve prolapse. Initial symptoms resolved spontaneously without therapy, but fever recurred with associated arthralgias, myalgias, diffuse and worsening lymphadenopathy, splenomegaly, and bilateral pulmonary infiltrates. INVESTIGATIONS: Physical examination, blood and urine cultures, MRI of the spine, echocardiogram, extensive serologies, serum and urine protein electrophoresis, immunofixation electrophoresis, bone-marrow aspiration and biopsy with flow cytometry, cytogenetics, and gene rearrangement studies, CT scan of the chest, abdomen and pelvis, whole-body PET, and lymph-node biopsy for histological examination, immunohistochemistry, and gene rearrangement studies. DIAGNOSIS: Angioimmunoblastic T-cell lymphoma. MANAGEMENT: Steroids (prednisone, methylprednisolone), levofloxacin, isoniazid with pyridoxine, ciclosporin A, methotrexate, alemtuzumab, broad-spectrum antibiotics, Pneumocystis carinii prophylaxis, vancomycin, and clindamycin.

Linfadenopatía angioinmunoblástica: fisiopatología, citogenética, histología y tratamiento / Angioimmunoblastic lymphadenopathy: physiopathology, cytogenetic, histology and treatment

La linfadenopatía angioinmunoblástica, a pesar de ser clínicamente similar a la enfermedad de Hodking, es una entidad hiperinmune distinta, aparentemente de linfocitos B. Es una enfermedad caracterizada por síntomas constitucionales y linfadenopatía. El diagnóstico se establece mediante biopsia del ganglio linfático, con la cual se observan alteraciones en la morfología del mismo, ausencia de centros germinativos, arborización de vénulas poscapilares y un infiltrado polimorfo que incluye inmunoblastos. Los hallazgos de laboratorio incluyen, anemia hemolítica autoinmune e hipergammaglobulinemia policlonal

Angioimmunoblastic lymphadenopathy (AILD) with benign course.

A group of rare systematic lymphoproliferative disorders have been described under the heading of angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD), from purely reactive to bona fide malignancies. Some patients exhibit a benign form of disease, but most exhibit an aggressive form with high mortality rate. We present two elderly patients with prominent constitutional symptoms, generalized lymphadenopathy, hepatosplenomegaly, diffuse maculopapular rash, polyclonal hypergammaglobulinaemia and immunohaemolytic anaemia. Lymph node biopsies showed features consistent with the diagnosis of AILD. The patients were treated with steroid and they are in complete remission 3.5 and 2.5 years, respectively after the diagnosis has been established.

Síndrome de Gianotti-Crosti: informe de 18 casos / Gianotti-Crosti syndrome: report of 18 cases

En el presente estudio se presentan 18 casos de síndrome de Gianotti-Crosti, que se documentaron de marzo de 1987 a noviembre de 1994, en el Hospital Regional No. 1 de Acapulco, y en el hospital General de Zona No. 14 de guadalajara del Instituto Mexicano del Seguro Social (IMSS). Se describen algunas características epidemiológicas, las manifestaciones clínicas y morfológicas y los hallazgos histipatológicos de laboratorio de la enfermedad

Acute lymphadenopathy complicating quinidine therapy.

A patient is described with quinidine-induced acute lymphadenopathy syndrome proven by rechallenge of the drug. Serum markers for systemic lupus were negative.

Prognostic factors in angioimmunoblastic lymphadenopathy.

In order to identify prognostic factors in angioimmunoblastic lymphadenopathy (AIL), 30 directly diagnosed patients were prospectively followed for more than 42 months. Age and sex distribution, clinical and laboratory findings and evolution were not different from previously reported series. Median duration of survival was 24 months. Parameters associated with a longer survival in our series were localized adenopathies (P = 0.01) and the achievement of a remission (P less than 0.0001). Features associated with a shorter survival included drug exposure in relation to the onset of the disease (P = 0.02), rash (P less than 0.0001), lymph node eosinophilia (P = 0.03) and elevated serum lactic dehydrogenase (P = 0.03). Drug exposure and rash were, however, significantly dependent (P = 0.02). In addition, lymphopenia, the presence of circulating immune complexes, and the absence of polyclonal hypergammaglobulinemia may indicate a poor prognosis, although the significance level is not achieved in this short series. None of the parameters tested was significantly related to the lymphomatous transformation of AIL, which occurred in four cases. It is concluded that multicentric prospective studies of AIL are necessary in order to better define this disorder, to find prognostic factors, and to optimize therapy.

Angioimmunoblastic lymphadenopathy in a child with unusual clinical and immunologic features.

We report a case of angioimmunoblastic lymphadenopathy in a child followed for 13 years. Unusual features include prolonged course, cold urticaria, nonthrombocytopenic purpura, poor wound healing, transfusion reactions, and possible neurologic involvement with cerebritis and epileptic seizures. The patient's serum contained a monoclonal cryoglobulin, immunoglobulin G, kappa light chain type, that activated the classic complement pathway in vitro and mediated passive transfer of the cold urticaria. The patient responded well to corticosteroids and has been in clinical remission for 8 years without specific treatment. There is immunologic evidence of persistent residual disease activity. This case illustrates the remarkable diversity of clinical and immunologic features and the variable prognosis of this disorder.

Extramedullary hematopoiesis. A cause of severe generalized lymphadenopathy in agnogenic myeloid metaplasia.

Although microscopic evidence of extramedullary hematopoiesis in lymph nodes is a frequent finding in autopsy studies of patients with agnogenic myeloid metaplasia, clinically significant lymphadenopathy is a rare occurrence. In this article we describe an unusual case of severe generalized lymphadenopathy and lymphedema secondary to extramedullary hematopoiesis in multiple lymph nodes. With the use of low-dose radiotherapy, both the lymphadenopathy and lymphedema resolved.

Unexplained persistent lymphadenopathy in homosexual men and the acquired immune deficiency syndrome.

Ninety-three homosexual men with persistent lymphadenopathy were followed at the Memorial Sloan-Kettering Cancer Center for a mean period of 20.8 months. Histories and serologic evidence of a number of previous infections were common, but the lymphadenopathy was not due to recognizable infections or neoplastic disease. Leukopenia, lymphopenia, granulocytopenia, monocytopenia, decreased ratios of T-helper to T-suppressor cells, decreased natural killer cell activity and increased serum immunoglobulin concentrations were common. Lymph node biopsies showed reactive hyperplasia without any unique histopathologic features. Antibody to the human T-lymphotropic virus-III (HTLV-III or LAV), a newly described retrovirus believed to be the etiologic agent of the acquired immune deficiency syndrome (AIDS), was detected in 91.4%. Over a 3-year period, 11 cases of AIDS were recognized in these patients: Kaposi's sarcoma developed in 7 and opportunistic infections in 4. The lymphadenopathy resolved in six patients and the others remained unchanged. Although most of these patients are asymptomatic and remain well, the risk of AIDS in this group of men was higher than in other groups of homosexual men in New York.

Pulmonary involvement in angioimmunoblastic lymphadenopathy following autoimmune disease.

A 44-year-old woman presented with a systemic illness characterized by a rash, polyarthritis and hypothyroidism. She later developed angioimmunoblastic lymphadenopathy (AIL) which became progressively resistant to chemotherapy. Pulmonary features were prominent throughout her illness and included pleural effusions, hilar adenopathy and parenchymal infiltrates. Lung histology showed a transition from nonspecific chronic inflammation with fibrosis to a polymorphic cellular infiltrate typical of AIL. Immunological features included a low C3 level, hypogammaglobulinaemia and depressed cell-mediated immunity.