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[Bronchoscopy in the diagnosis of diffuse pulmonary infiltrates, and corticosteroid treatment in patients with acute respiratory failure].

Forty patients with acute respiratory failure underwent fiberoptic bronchoscopy for evaluation of diffuse pulmonary infiltrates. Immunohematological diseases were the commonest underlying conditions; they were present in 48% of patients. Twenty-five percent of patients had pulmonary disease. Fiberoptic bronchoscopy was done 2.2 days after confirmation of the pulmonary lesion. Seventy-three percent of patients had already received antibiotics and 28% required mechanical ventilation at the time of fiberoptic bronchoscopy. Arterial blood gas analysis done just before fiberoptic bronchoscopy revealed that PaO2 and PaCO2 were 62 Torr and 36 Torr, respectively. A specific diagnosis was made in 29 patients (73%): pneumonia in 13; pulmonary fibrosis in 4; summer-type hypersensitivity pneumonitis in 3; and leukemic cell infiltration in 2. Fifty-two percent of patients were successfully treated with specific therapy. The complications of fiberoptic bronchoscopy were bleeding in 3 patients, pneumothorax in 3 patients, and exacerbation of respiratory failure in one patient. There were no procedure-related deaths, and fiberoptic bronchoscopy was judged to be safe and useful in the diagnosis of pulmonary infiltrates in patients with acute respiratory failure. Twenty-five patients (68%) received high doses of methylprednisolone. The average initial dose was 851 +/- 373 mg, and more than 100 mg was administered for 8 +/- 6 days. Seventeen of these patients recovered from the pulmonary disease. A controlled randomized study is needed to reevaluate the role of corticosteroids in the treatment of acute respiratory distress syndrome.

Acute Disease↗

Immunoperoxidase techniques in the evaluation of cutaneous lymphocytic infiltrates.

The widespread availability of immunoperoxidase technology and antibody probes over the past 15 years has changed the discipline of dermatopathology. In no aspect is this more evident than in the microscopic study of cutaneous lymphoid infiltrates. In the following review, the discussion focuses on some of the ways in which immunophenotyping is used to enhance the diagnosis of cutaneous lymphoproliferative disorders. A strategy for the use of immunophenotyping in some common clinical situations is forwarded. The immunopathologic findings can be helpful in resolving problems in the differential diagnosis of lymphoma and mimics of lymphoma.

Diagnosis, Differential↗

Chronic myelomonocytic leukemia revealed by uncontrollable hematuria.

Nephrectomy was performed for uncontrollable unilateral hematuria in an apparently healthy 72-year-old man. The suburothelial connective tissue of the kidney was infiltrated by primitive myeloid cells with associated acute vasculitis and foci of extramedullary hematopoiesis. Subsequently, the patient was shown to have chronic myelomonocytic leukemia. Although renal involvement and vasculitis have been recorded previously in chronic myelomonocytic leukemia, this is the first occasion, to our knowledge, where their concurrence resulted in such a spectacular presentation.

Aged↗

Skin involvement in myelogenous leukemia: morphologic and immunophenotypic heterogeneity of skin infiltrates.

A systematic morphological analysis of cutaneous infiltrates in acute myelogenous leukemia and myelodysplastic syndrome revealed that in many cases the infiltrating cells have a different phenotype from those in the bone marrow. This study sought to answer two questions: (a) How wide is the range of cytological features and immunoreactivity of the cutaneous infiltrates and what danger is there of misinterpretation? (b) What are the possible causes of the wide spectrum of differentiation of the cells infiltrating the skin? Skin biopsy specimens from 16 patients with myelogenous leukemia or myelodysplastic syndrome were investigated. The diagnosis was acute myelomonocytic leukemia (M4, according to the French-American-British/FAB system of classification of acute leukemias) in eight cases, acute monocytic leukemia (M5) in four cases, aleukemic leukemia cutis as a recurrence of M2 leukemia after treatment in one case, and myelodysplastic syndrome in three cases, including one case of myelodysplasia with an excess of bone marrow blasts (RAEB-T) and two cases of chronic myelomonocytic leukemia, one of which presented as aleukemic leukemia cutis. Reactivity with the macrophage-associated antibodies anti-CD68, Ki-M1p, and anti-lysozyme was the most consistent. However, the naphthol AS-D chloroacetate esterase reaction and staining with DAKO-M1, Ki-My2p, anti-neutrophil elastase, and anti-CD34 were found to be of little value for identifying the cutaneous infiltrate as myelogenous. Some antibodies (e.g., anti-S100 protein and MB2) even produced staining in a few cases that could have led to a mistaken diagnosis of histiocytic neoplasm or malignant lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Presenting Cells↗

Testicular infiltration in acute myeloid leukemia with complex karyotype including t(8;21).

Testicular infiltration is a well-known complication in acute lymphoblastic leukemia. In acute myeloid leukemia (AML), it has rarely been described and preferably occurred in cases with myelomonocytic or monoblastic differentiation. We report on a patient with AML with complex karyotype including translocation t(8;21) who presented with testicular infiltration at the time of his third bone marrow relapse. Cytological analysis of the specimen showed infiltration with blasts displaying the typical morphology of AML with translocation t(8;21) and comparable to those detected in the bone marrow. Fine needle aspiration cytology might suffice in these cases and should be performed if testicular involvement is suspected.

Acute Disease↗

Bilateral epibulbar granulocytic sarcomas: a case of an 8-year-old girl with acute myeloid leukaemia.

PURPOSE: An 8-year-old girl with a history of acute myeloid leukaemia (AML) presented with bilateral ocular discomfort, conjunctival injection, photophobia, and epiphora. METHODS: Clinical examination and high-frequency ultrasound showed bilateral epibulbar tumours. RESULTS: Granulocytic sarcomas were suspected and leukaemic infiltration was confirmed by fine-needle aspiration biopsy based cytopathologic examination. CONCLUSIONS: Epibulbar granulocytic sarcoma in AML is rare (particularly in a child). We describe the first high-frequency ultrasound images and illustrate the use of a minimally invasive fine-needle aspiration biopsy technique to confirm our diagnosis.

Biopsy, Needle↗

Breast infiltration by acute lymphoblastic leukemia during pregnancy.

A case of bilateral breast infiltration as the initial manifestation of FAB-L3 leukemia during pregnancy is reported. This rare presentation is usually associated with Burkitt's lymphoma or FAB-L3 leukemia. A high suspicion of the presence of hematologic malignancy and appropriate evaluation are indicated in the presence of this clinical manifestation.

Adult↗

Isolation of tumor-specific cytotoxic CD4+ and CD4+CD8dim+ T-cell clones infiltrating a cutaneous T-cell lymphoma.

We have isolated several T-cell clones from lymphocytes infiltrating a human major histocompatibility class (MHC) II negative cutaneous T-cell lymphoma (CTCL). We describe here two of these clones, TC5 and TC7, with, respectively, a CD4(+)CD8dim+ and CD4(+)CD8(-) phenotype. Both clones mediated a specific MHC class I-restricted cytotoxic activity toward the fresh autologous tumor cells, and autologous tumor cell lines previously established with interleukin-2 (IL-2) and IL-7 from the skin and from the blood. Analysis of the T-cell receptor (TCR) Vbeta gene expression showed that the tumor cells, which were shown to have a trisomy 7 by fluorescent in situ hybridization, expressed Vbeta7/Jbeta2.3, Vbeta13/Jbeta2.5, and Vbeta22/Jbeta2.5 rearrangements. Phenotypic analysis using specific anti-Vbeta monoclonal antibodies indicated that only Vbeta13 could be detected on the cell membrane of the tumor cells. Analysis of the TCR Vbeta gene expression of the clones showed that TC5 and TC7 expressed a unique TCR-Vbeta transcript, corresponding, respectively, to Vbeta5/Jbeta2.3 and Vbeta17/Jbeta2.7 gene segments. To determine whether these reactive T lymphocytes were present in vivo, we used specific primers corresponding to TC5- and TC7-Vbeta TCR transcripts. The results showed that both cytotoxic T-cell clones were present at the lesional skin site and amplified in vitro. TC7 was found in the patient peripheral blood invaded by tumoral cells, whereas TC5 was not, indicating that the repertoire of the reactional lymphocytes differs in the blood and at the tumor site. These results show for the first time the presence of reactive T lymphocytes with CD4 or double-positive phenotype infiltrating a CTCL. These findings raise the question of the role of these antitumoral effector T cells in the tumor growth.

Aged↗

Infantile leukemia presenting with cholestasis secondary to massive pancreatic infiltration.

We present a 10-week-old infant who presented with cholestasis. Biliary obstruction secondary to massive pancreatic infiltration was demonstrated by ultrasound. A diagnosis of acute lymphoid leukemia was confirmed. Enlargement of the pancreas is unusual both in this age group and in leukemia. Infantile leukemia, although rare and usually not associated with gastrointestinal presentations, should be considered as a cause of pancreatic enlargement and neonatal cholestasis.

Cholestasis, Intrahepatic↗

Extensive neoplastic cardiac infiltration in a patient with acute myelogenous leukemia: role of echocardiography.

We present the case of a 34-year-old man with a history of relapsed acute myelogenous leukemia with extensive metastatic infiltration of the endomyocardium. Transesophageal echocardiography revealed masses within all the cardiac chambers and associated vascular structures. Biopsy of the superior vena cava mass had the histological features of a granulocytic sarcoma (GS, chloroma). Massive involvement of the heart with GS is very rare, and only a few reports have been published in the literature.

Adult↗

[Successful radiotherapy for the thoracic cord infiltration of adult T-cell leukemia/lymphoma].

A-51-year-old woman with a sixteen-year history of mixed connective tissue disease was admitted to the Kitasato University Hospital because of hypogastric pain in September 1999. Colonofiberscopy and computed tomography in the abdomen demonstrated thickening of the intestinal wall with a hemorrhagic ulcer in the terminal ileum. The histopathologic findings of the lesion revealed diffuse infiltration of atypical T-lymphocytes. The titers of anti-HTLV-I antibody and serum soluble IL-2 receptor were elevated. The diagnosis of adult T-cell leukemia/lymphoma (ATLL) infiltrating the terminal ileum was made. Combination chemotherapy including VEPA-M was undertaken, and resulted in a partial response. ATLL became refractory about June 2000. Flaccid paralysis, dysesthesia in the left lower limb and bladder-bowel disturbance emerged in a few days, July 2000. T2-weighed MRCT images demonstrated that a lesion with a high intensity signal was present in the spinal cord around Th 7. Flower-like cells were detected in the cerebrospinal fluid. Infiltration of ATLL into the thoracic cord was diagnosed. Administration of intrathecal methotrexate and prednisolone, systemic dexamethasone and local irradiation of 30 Gy improved the paralysis and the abnormal MRCT findings. Rehabilitation restored the patient's ability to walk.

Antineoplastic Combined Chemotherapy Protocols↗

Mucocutaneous manifestations of lymphomas and leukemias in black Kenyan children.

BACKGROUND: Childhood leukemia and lymphoma are common problems in Tropical Africa, including Kenya. Studies done in Western populations indicate that 25-50% of patients with leukemia and lymphoma have specific or nonspecific cutaneous signs. In dark-skinned patients, reports of such mucocutaneous manifestations are scarce. The lesions in these patients may easily be missed, if not specifically looked for. METHOD: Eighty-six indigenous Kenyan children with a confirmed diagnosis of leukemia or lymphoma were specifically examined for any mucocutaneous manifestations at presentation, during their treatment, and during subsequent follow-up. Whenever possible, an attempt was made to determine the causes of these lesions. All patients were given standard therapy for the primary hematologic disorder. RESULTS: Two-thirds of the patients had mucocutaneous symptomatology at presentation: 17.4% had skin infiltration by the malignant cells. During therapy an even larger number developed nonspecific skin manifestations. Most of these were the result of myelosuppression, immunosuppression, or direct cytotoxic effects on tissues. CONCLUSIONS: Mucocutaneous manifestations in black children with leukemia and lymphoma are very common.

Acute Disease↗

Secondary cutaneous infiltration in B cell chronic lymphocytic leukemia.

We describe a patient presenting with B cell chronic lymphocytic leukemia (B-CLL) who subsequently developed cutaneous infiltrates. Specimens of the blood, bone marrow and cutaneous infiltrations all showed the same heavy-chain gene rearrangement. Following failure of conventional chemotherapy, and in view of the similarity of the disease to cutaneous T cell lymphoma, interferon-alpha therapy was employed with satisfactory results. Introduction of this cytokine to the therapeutic modalities for secondary cutaneous B-CLL would hopefully change the poor outcome of this entity, or at least could produce a better quality of life. Loss of histidine decarboxylase activity in the infiltrating cells - in contrast to circulating lymphocytes - may be associated with the transformation of B-CLL to a more aggressive infiltrative form, offering a possible explanation for tissue invasiveness. The changing character of the disease raises the possibility of a second mutational event in the course of B-CLL.

Antineoplastic Combined Chemotherapy Protocols↗

HTLV-I associated cutaneous T-cell lymphoma--report of a case with atypical clinical presentation.

A case of a 20-years-old black man from Salvador, Bahia with HTLV-I associated T cell lymphoma is presented. In spite of the absence of splenomegaly and leukemia, the patient had a marked cephalic tumoral infiltration associated with axillary tumors in a pattern not yet described in adult T cell lymphoma. Peripheral blood involvement was observed later on in the course of the disease. The patient underwent chemotherapy but died seven months after diagnosis.

Adult↗

[A case of complete remission following recurrent relapses 12 years after onset of acute myelocytic leukemia. Response to protocol including neocarzinostatin].

A 23-year-old male who had suffered recurrent relapses of acute myelocytic leukemia was treated with a protocol including neocarzinostatin (NCS) and complete remission was obtained. At the age of 11 years, he had complained of general fatigue and anemia, and was diagnosed as having AML because of the presence of leukemic cell infiltration in the bone marrow as well as peripheral blood. Auer bodies and a positive reaction to peroxidase were found. The last episode of relapse occurred at the age of 15 years, when he achieved complete remission following a trial protocol which included NCS. NCS seemed to be effective after it had been used intravenously for a short time. The patient has maintained complete remission for the past 7 years and has had no consolidation therapy in the last 3 years. For the last 18 months, he has been working in a market as a clerk 8 hours a day. NCS with a rapid infusion time seems to have effects on leukemic cells when it used with proteolytic enzyme. Neither skull radiation nor testicular biopsy were attempted. Results of CSF examination were within normal limits, but EEG and CT scan revealed the probability of early-stage leukoencephalopathy, although no significant clinical signs were observed. He had suffered an asthmatic attack before the onset of AML, but no further attack occurred until several months ago. In order to establish any relationship between these two diseases, further detailed analysis will be necessary.

Adult↗

Pancreatic tumor formed by infiltration of adult T-cell leukemia cells.

CONCLUSION: We have described a case of pancreatic tumor formed by adult T-cell leukemia (ATL) cell infiltration. BACKGROUND: The patient was diagnosed as chronic ATL hematologically with the findings of increased number of atypical lymphocytes, ATL cells in the peripheral blood, and positive human T-cell leukemia virus type I (HTLV-I) antibody in the serum. The pancreatic tumor was identified by ultrasonography and computed tomography as a diffusely swollen tumor from the body to the tail of the pancreas. Biopsy specimen confirmed the ATL cell infiltration into the pancreas immunohistochemically, and Southern blot analysis showed the integration of HTLV-I proviral DNA both in the pancreas and in the peripheral blood. RESULTS: The pancreatic tumor diminished spontaneously without chemotherapy when ATL cells in the peripheral blood disappeared by spontaneous regression.

Aged↗

Characterization of in vitro migratory properties of anti-CD19 chimeric receptor-redirected CIK cells for their potential use in B-ALL immunotherapy.

OBJECTIVE: Cytokine-induced killer (CIK) cells are ex vivo expanded cells enriched in CD3(+)CD56(+) natural killer T (NKT) cells with major histocompatibility-unrestricted cytotoxicity against several tumoral targets, except B-lineage acute lymphoblastic leukemia (B-ALL). We redirected CIK cells cytotoxicity toward B-ALL with a chimeric receptor specific for the CD19 antigen and then explored if modified-CIK cells maintain the same chemotactic properties of freshly isolated NKT cells, whose trafficking machinery reflects their preferential localization into the sites of B-ALL infiltration. MATERIAL AND METHODS: CIK cells were expanded ex vivo for 21 days and analyzed for expression of adhesion molecules and chemokine receptors regulating adhesion and homing toward leukemia-infiltrated tissues. CIK cells were then transduced with the anti-CD19-zeta-internal ribosomal entry site-green fluorescent protein retroviral vector and characterized for their cytotoxicity against B-ALL cells in a (51)Cr-release assay and for their trafficking properties, including chemotactic activity, adhesion and transendothelial migration, and metalloproteases-dependent invasion of Matrigel. RESULTS: Similarly to freshly isolated NKT cells, CD49d and CD11a were highly expressed on CIK cells. Moreover, CIK cells expressed CXCR4, CCR6, and CCR7 (mean expression 72%, 60%, and 32%, respectively), presenting chemotactic activity toward their respective ligands. Anti-CD19 chimeric receptor-modified CIK cells became cytotoxic against B-ALL cells (mean lysis, 60%) and showed, after exposure to a CXCL12 gradient, high capacity to adhere and transmigrate through endothelial cells and to invade Matrigel. CONCLUSION: The potential capacity to localize into leukemia-infiltrated tissues of anti-CD19 chimeric receptor-redirected CIK cells, together with their ability to efficiently kill B-ALL cells, suggests that modified-CIK cells represent a valuable tool for leukemia immunotherapy.

Antigens, CD↗