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1/22. Management of pleural effusions in children with malignant lymphoma.

    PURPOSE: The aim of this study was to determine potential problems in the diagnosis and management of children with pleural effusions and malignant lymphoma as well as the efficacy of thoracentesis. methods: The case histories of six children with malignant lymphoma who presented with pleural effusions were reviewed. Thoracentesis was performed using the Seldinger technique. RESULTS: Four of the children presented with symptoms and chest radiograph findings similar to pneumonia. A large mediastinal mass was present in two children. Pleural fluid analysis resulted in a definitive diagnosis of lymphoma in five of the six children. Two of the children had symptoms of reexpansion pulmonary edema after removal of pleural fluid. An empyema developed in one child after thoracotomy and chest tube placement. Reaccumulation of pleural fluid was common before initiating chemotherapy. CONCLUSIONS: Malignant pleural effusions frequently are present in children with non-Hodgkin's lymphoma. They may present with respiratory distress because of the size of the effusion, the mediastinal mass, or both. Management of these pleural effusions is associated with potential complications, some of which are life threatening. Thoracentesis is the initial diagnostic and therapeutic procedure of choice. The use of a Seldinger technique for thoracentesis has proved useful and safe. In patients with large effusions, aggressive removal of the pleural fluid may be followed by reexpansion pulmonary edema.
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2/22. Primary pleural effusion posttransplant lymphoproliferative disorder: Distinction from secondary involvement and effusion lymphoma.

    pleural effusion presentation of posttransplant lymphoproliferative disorder (PTLD) is relatively uncommon. Most examples of effusion-based PTLD have been secondary to widespread solid organ involvement, and are associated with an aggressive clinical course. We report on a case of primary effusion PTLD in a 70-yr-old male liver transplant recipient with a history of hepatitis b infection. Cytomorphologically, the pleural fluid specimen showed a monomorphous population of intermediate to large-sized transformed lymphoid cells, with irregular multilobated nuclear contours and readily identifiable mitotic figures. Flow cytometric immunophenotypic studies revealed a CD5-negative, CD10-negative, lambda immunoglobulin light chain-positive, monoclonal B-lymphocyte (CD19-positive/CD20-positive) population. The immunocytochemical stain for CD30 antigen was negative. in situ hybridization study for Epstein-Barr virus (EBV) early rna (EBER) and Southern blot analysis for EBV terminal repeat sequences were both positive. Southern blot analysis for human herpes virus-8 (HHV-8) was negative. No solid-organ PTLD was identified, and the cytologic results supported the diagnosis of primary effusion PTLD. immunosuppression was decreased, and 8 mo following the diagnosis of pleural fluid PTLD, the patient was stable and his pleural effusion had markedly diminished. Recognition of primary effusion PTLD and its distinction from PTLD secondarily involving the body fluids and from other lymphomas is important, since the behavior and prognosis appear different.
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3/22. Chronic T-cell lymphoproliferative disease expressing natural killer cell receptors: clinicopathological and molecular features.

    The frequency and clinicopathological significance of the expression of natural killer cell receptors (NKRs) in T-cell malignancies remain undefined. A 71-year-old man presented with leukocytosis, generalized lymphoadenopathy, and hepatosplenomegaly. bone marrow and lymph node biopsies showed a T-cell lymphoproliferative disease expressing NKRs (CD2( ), CD3( ), CD4( ), CD5( ), CD7( ), CD8(-), CD56(-), CD94( ), CD158a( ), CD158b( ), CD161(-), p70(-), TCRalphabeta(1), TCRgammadelta(2), TIA-1(-)). An abnormal clone, 46,Y,add(X)(p14),der(1)t(1;6)(p33;p21),t(7;12)(p10;q10), was found on conventional karyotyping. comparative genomic hybridization confirmed these findings, and showed a deletion of 12p that was not apparent on karyotyping. Clinically, the disease remained indolent and responded transiently to purine analogs but not to intensive chemotherapy. Peripheral T-cell lymphoproliferative disease of CD4( )alphabeta(1)NKR( ) phenotype is hitherto undescribed. The issues of whether this case was derived from transformation of a rare T-cell subtype or represented aberrant T-cell expression of NK-cell antigens, and the clinicopathologic significance of these T-cell neoplasms warrant further studies.
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4/22. A large quantity of CD3-/CD19-/CD16- lymphocytes in malignant pleural effusion from a patient with recurrent cholangio cell carcinoma.

    Tumor infiltrating lymphocytes (TILs) are candidates for adoptive cellular immunotherapy. Here we report on a patient whose TILs presented unusual lymphocyte antigens. Pleural effusions were collected from a 47-year-old man with recurrent cholangio cell carcinoma and malignant effusion. Effusion-associated lymphocytes (EALs) were separated by ficoll-Hypaque gradient, and the EAL phenotype was determined by flow cytometry. The percentage of positive cells was determined for each lymphocyte-related differentiation antigen. The percentages of CD3 , CD19 , and CD16 lymphocyte subpopulations among EALs were 20%, 7%, and 3%, respectively. Nearly 70% of EALs were CD3-/CD19-/CD56-/CD16- cells. The phenotypes of peripheral blood lymphocytes (PBLs) collected simultaneously from the patient's peripheral blood were CD3 (52%), CD19 (20%), and CD16 (20%). When EALs were cultured in medium without pleural effusion, T cell-related antigens, but not B cell- or natural killer (NK) cell-related antigens, were newly expressed on EALs, and this expression reached a plateau after 48 h in culture. The proportions of CD3 , CD19 , and CD16 cells were 69%, 7%, and 3%, respectively. However, when EALs were cultured in medium with pleural effusion, increased expression of T cell-related antigens was not observed; the proportions of CD3 , CD19 , and CD16 cells were 16%, 6%, and 1%, respectively. Neither total cell numbers nor cellular viability of EALs changed significantly after in-vitro culture, suggesting that significant proliferation or death of EALs did not occur during the culture period. Co-culture of the patient's PBLs with autologous pleural effusion for 96 h did not alter the expression of lymphocyte-related antigens on the PBLs. These results indicate that expression of T cell-related antigens, but not B cell- or NK cell-related antigens, on EALs was blocked temporarily by the malignant pleural effusion. This is the first report concerning the existence of a large quantity of unclassified lymphocytes in which the T cell-related antigens were reversibly masked in the malignant pleural effusion.
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5/22. Doxil-induced regression of pleuro-pulmonary metastases in a patient with malignant meningioma.

    Metastatic meningioma is a rare disease, which has no effective chemotherapy. We report on a treatment of this condition with Doxil, a liposomal doxorubicin formulation. A 60-year-old woman with massive pleuro-pulmonary metastases from recurrent cranial meningioma was treated with Doxil (50-37.5 mg/m2) for 18 months with near-complete resolution of metastases and disappearance of pleural fluid. The only significant toxicities observed were stomatitis and hand-foot syndrome, which resolved with dose reduction and increase of dosing intervals. Doxil was cleared very slowly in this patient with a monoexponential half-life of 108 h. The patient remains in near-complete response for 6 months after treatment discontinuation. This is the first report on an effective chemotherapy in a patient with typical metastatic meningioma. The exact mechanism accounting for such an effective drug action is not clear, but may be related to a particularly high microvascular permeability to the liposome carriers in these metastatic lesions.
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6/22. Positive response to oral chemoendocrine combination therapy using 5"-deoxy-5-fluorouridine for locally advanced breast cancer with carcinomatous pleurisy: report of a case.

    A 60-year-old postmenopausal woman presented with an ulcerating and bleeding tumor in her right breast. On physical examination, the tumor was found mainly in the D area of the right breast, and was associated with ulceration and thoracic rigidity. Chest X-ray showed a pleural effusion in her right chest and a computed tomography scan after thoracentesis showed multiple bilateral pleural nodules. Thus, a diagnosis of unresectable advanced breast cancer (T4cN2M1b, PLE) was made. She was given oral 5"-deoxy-5-fluorouridine (5"-DFUR) with medroxyprogesterone acetate, followed by tamoxifen, without any severe adverse reactions, and was subsequently followed up as an outpatient. Her tumor gradually decreased in size, the thoracic rigidity disappeared, and the pleural dissemination and effusion resolved. Thereafter, a radical mastectomy was performed and histologically, the tumor was Grade 1a. She had no signs of recurrence or metastasis 14 months postoperatively. Therefore, oral chemoendocrine combination therapy with 5"-DFUR resulted in a favorable quality of life, there were no severe adverse reactions, and the patient was able to be managed as an outpatient.
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7/22. Detection of two cell populations corresponding to distinct maturation stages in API-2/MLT-positive mucosa-associated lymphoid tissue lymphoma cells proliferating in pleural effusion.

    A 66-year-old man was admitted to our hospital because of an intra-abdominal tumor and pleural effusion (PE). immunoelectrophoresis of the serum showed immunoglobulin m (IgM) kappa paraprotein (7330 mg/dL). Abnormal plasmacytoid cells were seen in both the peripheral blood (PB) and the bone marrow (BM). Computed tomography scans showed extensive thickening of the gastric wall and bilateral massive PE without lymph node or pulmonary involvement. A histologic examination of the gastric mucosa showed a diffuse infiltration of small- to medium-sized lymphoid CD20-bearing cells, some of which showed a plasmacytoid morphology. Lymphoepithelial lesions were demonstrated with an immunohistochemical stain. The diagnosis was gastric mucosa-associated lymphoid tissue (MALT) lymphoma infiltrating to the PE, PB, and BM. The PE contained numerous lymphoid cells with plasmacytoid morphology that Southern blotting analysis showed to have a monoclonal IgH gene rearrangement pattern. The cells seemed to be divided into two populations according to their surface markers: mature B-cells (CD19 CD20 CD22 CD21 CD38-) and secretory B-cells (CD19 CD20(dim)CD22-CD21-CD38 ). The reverse transcriptase-polymerase chain reaction technique detected the API-2/MLT transcript in the PE and PB. The patient had a good response to fludarabine treatment, which was followed with rituximab therapy. In general, gastric MALT lymphoma cells have a tendency to differentiate into plasma cells. In this article, we show that the cell character of API-2/MLT-positive MALT lymphoma is preserved even when the cells are disseminated. This is the first published case, to our knowledge, in which two differentiation stages of MALT lymphoma cells infiltrating into PE have been confirmed by flow cytometric analysis.
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8/22. central nervous system metastases of a pulmonary epitheloid haemangioendothelioma.

    The case of a 55-yr-old male with a right pleural effusion and multiple bilateral nodules is reported. A diagnostic thoracothomy was necessary to obtain a definitive histological diagnosis. During the postoperative course, the subject's neurological condition deteriorated and multiple cerebral mass lesions were discovered. The pathological analysis of both lung and cerebral tumours revealed an atypical endothelial cell proliferation; vascular immunohistochemical markers, such as factor viii and CD34, were strongly positive. His general condition remained poor and the patient died 18 months after the initial diagnosis. The final diagnosis was pulmonary epitheloid haemangioendothelioma with synchronous central nervous system dissemination, the first time the authors believe that association has been reported. Little is known of the prognosis and treatment of these tumours, due to their rarity. Negative prognostic factors appear to be the presence of symptoms, pleural effusion or multifocal presentations. Treatment should include surgical resection if possible; chemotherapy appears to have little effect. watchful waiting is an acceptable option, especially in asymptomatic patients.
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9/22. Agnogenic myeloid metaplasia with pleural extramedullary leukemic transformation.

    Agnogenic myeloid metaplasia (AMM) is one of the myeloproliferative disorders, and is usually accompanied by extramedullary hematopoiesis (EMH) in various organs, mainly in the liver, spleen and lymph nodes. Extramedullary hematopoiesis and/or leukemic transformation of EMH in the pleura is a rare occurrence and is usually asymptomatic. Pleural involvement is usually diagnosed on postmortem examination. Herein we describe a 71-year-old man with newly diagnosed agnogenic myeloid metaplasia who was evaluated for progressively worsening dyspnea, pulmonary hypertension and bilateral pleural effusions. EMH involving the lungs and pleura was suspected. A sulfur colloid technetium 99m bone marrow scan performed to detect extramedullary hematopoiesis was negative. The diagnostic thoracentesis yielded bloody fluid that contained a large population of myeloblasts, indicating pleural leukemic transformation. The patient received 100 cGy to the whole lung for treatment of pulmonary hypertension due to EMH. This was followed by 1500 cGy total dose of radiation to the left lung for pleural extramedullary leukemic transformation. Pleural effusions resolved and repeat echocardiography showed reduction of the pulmonary artery pressure. Three months later he had leukemic transformation involving the skin and lymph nodes. Four months after radiation therapy, he had full-blown acute myeloid leukemia. He received 2 cycles of Gemtuzumab ozogamicin (Mylotarg), allopurinol and hydroxyurea. Three months after initiation of chemotherapy, he deteriorated and received salvage chemotherapy of prednisone, VP-16 and imatinib mesylate (Gleevec). He was hospitalized for neutropenic fever and was diagnosed to have pulmonary aspergillosis. He died of multisystem failure 8 1/2 months after being diagnosed with AMM.
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10/22. Successful combination therapy with trastuzumab and paclitaxel for adriamycin- and docetaxel-resistant inflammatory breast cancer.

    We present a case of adriamycin-and docetaxel-resistant inflammatory breast cancer (IBC) in which partial response was achieved with combination therapy using trastuzumab and paclitaxel. A 48-year old woman noticed a lump in her right breast. She was diagnosed with IBC and the disease was staged as T4d N1 M0, stage III B. The patient was started on neoadjuvant chemotherapy with adriamycin (50 mg/m2) and docetaxel (60 mg/m2) administered every three weeks. Six courses were performed and the response was evaluated as no change. After one month, contralateral breast swelling indicated bilateral IBC. Bilatera1 mastectomy using the Halsted method was performed. The immunohistochemical results of the Hercep Test was strongly positive (3 ). After the mastectomy, right pleural effusion appeared, and cytological examination revealed the cells to be classV(adenocarcinoma). To treat the clinically advanced breast cancer, combination therapy with trastuzumab (initially 4 mg/kg followed by two or more cycles of 2 mg/kg) and paclitaxel (80 mg/m2) were given intravenously every week for eight cycles and then every two weeks thereafter. A total of 32 courses of therapy were performed, the pleural effusion completely disappeared and partial response was maintained for a duration of 482 days. The adverse reactions were mild, and it was possible for her to be treated as an outpatient with high quality of life. This report suggests that weekly combination therapy of trastuzumab and paclitaxel was useful for treatment of adriamycin-and docetaxel-resistant metastatic breast cancer.
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