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PubMed2000

Clinicopathological studies of a patient with adult T-cell leukemia and pseudogynecomasty.

We present a rare case of adult T cell leukemia/lymphoma (ATL) in which leukemic T cells expressed CD4 and CD25 surface antigens and infiltrated mammary glands during clinical course of the disease. A 40-year-old male was admitted with long-standing skin lesions and leukocytosis. Peripheral blood lymphocytes were highly pleomorphic and presented CD2, CD4, CD25, CD38 membrane surface antigens. The patient proved to be seropositive for human T-cell lymphotropic virus type I (HTLV-I) antibodies. Monoclonal expansion of lymphoid cells integrated with HTLV-I genome was observed, and the diagnosis of ATL chronic type was made. He underwent a chemotherapy regimen, and skin lesions and leukocytosis improved markedly. He progressed with an indolent clinical course of ATL, when he was admitted with bilateral hyperplasia of breast, recurrent skin lesions, and leukocytosis. Breast biopsy revealed bilateral gynecomasty, extensive leukemic infiltration of typical ATL cells in the mammary glands, and the presence of mammary epithelial cells productively infected with HTLV-I. This is the first report describing invasion of the mammary tissue with HTLV-I-transformed T-cells and HTLV-I-associated breast disease.

Breast↗
PubMedDate not supplied

Mouse L1210V leukemia as a model to analyse efficiency of leukemic cell elimination by immunotoxin, antibody and complement, and cytostatic agents.

In an attempt to eliminate selectively mouse L1210V leukemic cells from infiltrated bone marrow, the immunotoxin MoAb-16-RTA composed of monoclonal antibody recognizing oncofetal antigen on L1210V cells and the ricin A chain was prepared. The immunotoxin exhibited an antigen-specific, dose-dependent cytotoxic effect in vitro. One hour's exposure of leukemic cells to 10(-6) M of immunotoxin appeared to be sufficient to kill all leukemic cells. In the experimental conditions applied, a complete elimination of L1210V cells from leukemic bone marrow was achieved. MoAb-16 antibody and complement in the same experimental protocol, the bone marrow purging was not complete. The surviving leukemic cells were still able to grow and kill recipient mice. The in vitro exposure to immunotoxin or to antibody and complement was not toxic to normal bone marrow progenitors. The exposure of leukemic cells to selected cytostatic agents of the oxazaphosphorine group appeared to be effective in the elimination of leukemic cells, but doses required for killing leukemic cells were highly toxic to normal bone marrow progenitors.

Animals↗
PubMed1998

"Aleukemic" granulomatous leukemia cutis.

Aleukemic leukemia cutis is a rare condition characterized by the infiltration of the skin by leukemic cells before their appearance in the peripheral blood. The authors report a case of aleukemic leukemia cutis in a 30-year-old seemingly healthy man who presented with multiple skin papulonodular lesions and lack of peripheral blood involvement. Histopathologically, the skin infiltrates showed prominent granulomatous features that masked the underlying malignant process. Immunophenotypic studies of skin and bone marrow infiltrates revealed the myelomonocytic lineage of the atypical cells, consistent with M4 acute myelomonocytic leukemia. The authors emphasize the value of immunohistochemical studies in diagnosing a cutaneous atypical infiltrate and discuss problems of histopathologic differential diagnosis.

Adult↗
PubMed1988

Optic neuropathy in chronic lymphocytic leukemia.

Ophthalmic and neurologic involvement in chronic lymphocytic leukemia is uncommon, and if it does occur, it is usually only late in the course of the disease. We report three cases in which progressive visual loss from optic nerve infiltration was an early clinical manifestation of chronic lymphocytic leukemia. Progressive optic atrophy with loss of acuity and visual field occurred in all cases, preceded in one patient by transient visual obscurations and disc edema. Surface marker studies of cerebrospinal fluid lymphocytes were useful in differentiating leukemic optic nerve infiltration from other causes of optic nerve damage. Optic nerve irradiation gave considerable clinical improvement in all three cases.

Aged↗
PubMed2004

Adult T-cell leukemia predominantly involving exocrine glands.

OBJECTIVES: We describe a rare case of adult T-cell leukemia (ATL) presenting with dry mouth and swelling of bilateral parotid and submandibular glands. The unusual involvement of these exocrine glands by malignant cells prompted us to conduct a detail characterization of these infiltrating and circulating leukemic T cells, which may provide insight to the pathogenesis of exocrine involvement in ATL. METHODS: Immunophenotyping of peripheral ATL cells and microscopic examinations of various organs prepared by autopsy were performed. Analysis of the repertoire of T-cell receptor (TCR) of parotid gland-infiltrating ATL cells using molecular and immunohistochemical examinations were also performed. RESULTS: Microscopic examinations of various organs prepared by autopsy revealed the predominant and specific exocrine gland infiltration of ATL cells. Reverse transcription-polymerase chain reaction (RT-PCR) followed by both TCR spectratyping and complementary determining region (CDR)-3 sequencing analysis of TCR Vbeta of parotid gland-infiltrating T cells revealed a relatively restricted but not single usage of TCR Vbeta. Immunohistochemical analyses of parotid gland specimens detected only a small number of TCR Valphabeta-positive cells in parotid gland-infiltrating ATL cells. CONCLUSIONS: The predominant infiltration of ATL cells in exocrine glands implied that these T cells recognized exocrine gland-specific antigen. However, the absence of both TCR Vbeta mRNA transcripts and TCR Valphabeta protein expression in most ATL cells suggested that antigen recognition via TCR may not have played a major role in adhesion and subsequent infiltration into the exocrine glands in this patient. These results provide important background information to further elucidate the pathogenesis of exocrine gland-specific inflammation.

Aged↗
PubMed1995

c-KIT expression enhances the leukemogenic potential of 32D cells.

The growth of human leukemic cells in culture and in vivo is dependent upon the presence of hematopoietic growth factors. Most populations of human leukemic acute myeloblastic leukemia (AML) cells express c-Kit on their surface and respond to Kit ligand (KL) in culture. To determine if this interaction was of potential significance in vivo we used a mouse model system. 32D cells, a murine IL-3-dependent myeloid cell line, were rendered KL responsive by transfection of the murine c-Kit. After injection of 32D or 32D-Kit cells into syngeneic hosts, animals bearing 32D-Kit cells, but not 32D cells, became moribund and were killed. These animals had circulating leukemic blast cells, infiltration of bone marrow, spleen, brain, liver, lung, and kidney. Cells recovered from some of the animals continued to be dependent upon IL-3 or KL for growth while in other cases the cells were factor independent. This model illustrates that the constitutive expression of c-Kit enhances the leukemic potential of 32D cells. The model will be useful for studying the progression of leukemia in vivo and testing whether interruption of the interaction of Kit and KL can affect the growth of leukemic cells.

Amino Acid Sequence↗
PubMed1990

Recovery of megakaryocytopoiesis in vitro in children with acute lymphoblastic leukemia during induction of remission.

In children with acute lymphoblastic leukemia (ALL), megakaryocytopoiesis was investigated in vitro by the semisolid agar culture technique. In untreated ALL the median number of committed megakaryocyte progenitor cells (CFU-Mk) in the bone marrow was 2 (range less than 0.1-8) per 10(5) bone marrow cells instead of 30 (range 14-93) in controls, the impairment being dependent on the degree of leukemic bone marrow infiltration. However, if the number of CFU-Mk was related to residual nonleukemic bone marrow cells only, two-thirds of the children investigated had a frequency of CFU-Mk within the normal range. After 2 weeks of induction therapy the majority of the children had a low number of CFU-Mk in the bone marrow (median 6, range 0.5-40), a fact that could no longer be explained by a dilution of CFU-Mk by leukemic cells. After 4 weeks of chemotherapy (day 29) the frequency of CFU-Mk had risen to 18 (range 3-67) per 10(5) bone marrow cells, a value still significantly (p less than 0.01) below the normal range. In contrast to the changes in the number of CFU-Mk the median cell number per megakaryocyte colony remained constant during induction of remission. After cessation of long-term chemotherapy all children investigated had a normal number of CFU-Mk, suggesting that no permanent chemotherapy-related damage to committed megakaryocyte progenitor cells was induced.

Adolescent↗
PubMed2002

In vivo administration of vascular endothelial growth factor (VEGF) and its antagonist, soluble neuropilin-1, predicts a role of VEGF in the progression of acute myeloid leukemia in vivo.

Recent findings implied that the progression of hematologic malignancies, like that of solid tumors, is dependent on neovascularization. Recent studies on patients with acute myeloid leukemia (AML) showed increased levels of leukocyte-associated vascular endothelial growth factor (VEGF) and neovascularization of the bone marrow. Murine (32D, M1) and human (HEL, U937, and UKE-1) leukemic cell lines and freshly isolated leukemic cells were analyzed for the expression of VEGF and VEGF receptor mRNA. The expression of VEGF and VEGF receptors KDR and neuropilin-1 (NRP-1) was detected in these cells. In a murine chloroma model, delivery of VEGF(165) using microencapsulation technology resulted in enhanced tumor growth and vascularization, whereas treatment with a VEGF antagonist soluble NRP-1 (sNRP-1) inhibited tumor angiogenesis and growth. In a systemic leukemia model, survival of mice injected with adenovirus (Ad) encoding for Fc-sNRP-1 (sNRP-1 dimer) was significantly prolonged as compared with mice injected with Ad-LacZ. Further analyses showed a reduction in circulating leukemic cells and infiltration of liver and spleen as well as bone marrow neovascularization and cellularity. Taken together, these results demonstrate that angiogenic factors such as VEGF promote AML progression in vivo. The use of VEGF antagonists as an antiangiogenesis approach offers a potential treatment for AML. Finally, our novel in vivo drug delivery model may be useful for testing the activities of other peptide antiangiogenic factors.

Acute Disease↗
PubMed1993

Respiratory symptoms, lung function tests, airway responsiveness, and bronchoalveolar lymphocyte subsets in B-chronic lymphocytic leukemia.

A respiratory questionnaire was completed and spirometry, tests for lung volumes, diffusion capacity for CO, and methacholine bronchial challenge were performed in 24 outpatients with B-chronic lymphocytic leukemia (B-CLL), aged 44-79, presenting in different stages of their disease. In 10 patients, bronchoalveolar lavage (BAL) fluid was also obtained. Ten of twenty-four patients had symptoms consistent with chronic bronchitis, unrelated both to smoking history and to the clinical stage. Abnormal values (< 2 SD) were found in 4 patients for total lung capacity (TLC), in 9 for vital capacity (VC), 8 for forced expiratory volume in 1 sec (FEV1), 11 for MEF50, 15 for MEF25 and in 7 for diffusing capacity for carbon monoxide. Seven of nineteen patients had PD20FEV1 at less than 1,600 micrograms of methacholine chloride. There was a significantly negative correlation between white blood cell count and VC (r = 0.41, P < 0.05). A positive correlation was found between PD20FEV1 and FEV1/VC (r = 0.61, P < 0.01). The mean and SEM for BAL cells/ml was 463 (71.8) x 10(3). No leukemic cells but a marked increase in T lymphocytes (32.5 +/- 7.8%) were found in BAL fluid. There were significantly negative correlations between the number of BAL CD3+ T lymphocytes and PD20FEV1 (r = 0.61, P < 0.05), and between the number of BAL CD8+ T lymphocytes and PD20FEV1 (r = 0.84, P < 0.01). In conclusion, patients with B-CLL have a high prevalence of respiratory symptoms, small airway dysfunction and CD8 "alveolitis" related to airway responsiveness; despite the well-known lung interstitial lymphocyte infiltration in B-CLL, leukemic cells are not found in BAL fluid.

Adult↗
PubMed1998

[Localized pulmonary infiltration in chronic myelomonocytic leukemia].

A 38-year-old woman who had been treated for refractory anemia was admitted with severe pancytopenia, persistent fever and splenomegaly in May 1995. The bone marrow biopsy revealed hyperplastic marrow with marked fibrosis. Shortly after admission, cardiac tamponade developed. Though low-dose Ara-C therapy successfully controlled the tamponade, no hematological recovery was obtained. Then a chemotherapy consisted of Ara-C, acrarubicin and M-CSF was done and the neutropenia was improved. However, progressive leukocytosis with monocytosis and splenomegaly subsequently developed. Thus, the disease was considered to progress to CMML. Localized pulmonary infiltrates associated with a cavity, a pulmonary artery aneurysm and a recurrent high fever developed in October 1995. Though invasive pulmonary aspergillosis was suspected, blood and sputa culture, as well as serological tests were negative. In February 1996, massive hemoptysis occurred and the patient died due to respiratory failure after an emergency right lobectomy of the lung. Pathological examination of the operated lung disclosed that the localized pulmonary infiltrates consisted of monocytoid cells. Infiltration of the monocytoid cells in the tissue surrounding the pulmonary aneurysm was also observed. However, no pathologic organisms were detected at all. Thus, the leukemic cells were considered to have infiltrated locally into the lung.

Adult↗
PubMed1984

CT findings in leukemia.

Review of 84 computed tomographic (CT) scans in leukemic patients demonstrated a wide spectrum of abnormalities. Findings caused by leukemia were lymphadenopathy, visceral enlargement, focal defects, and tissue infiltration. Hemorrhage was by far the most common complication and could usually be characterized on the noncontrast CT scan. The distinction between old hematomas, foci of infection, and leukemic infiltration could not be made with certainty without CT-guided aspiration. Unusual instances of sepsis, such as microabscesses of the liver and typhlitis, were seen.

Adult↗
PubMed1982

Leukemic cell lysis pneumonopathy. A complication of treated myeloblastic leukemia.

The course of acute noninfectious pulmonary infiltrates in five patients with myeloblastic leukemia was evaluated. All had circulating blast cells (range, 245-192,000/mm3) and recently had received chemotherapeutic drugs for their leukemia. Within four days of the nadir of their leukocyte counts, a patchy, often multilobar pneumonitis developed. Cultures for bacteria, fungi, and viruses were all negative, and no clinical response was observed to broad-spectrum antibiotics. On lung biopsy, pathologic changes were characterized by diffuse alveolar damage with degenerating blast cells in the interstitium and in organizing alveolar exudates. No potential pathogenic organisms were seen on light or electron microscopy of the biopsy samples. In each case the pulmonary infiltrate resolved without specific therapy. We postulate that lysis of leukemic cells, with subsequent release of their enzyme contents, led to the diffuse alveolar damage observed pathologically. Leukemic cell lysis pneumonopathy may be one of the potential causes of pulmonary infiltrates in leukemic patients and can be distinguished pathologically by its distinctive pattern.

Adult↗
PubMed1978

Hodgkin's disease terminating in a T-cell immunoblastic leukemia.

A patient who developed an immunoblastic leukemia of T-cell type two and one half years after initial diagnosis of mixed cellularity Hodgkin's disease, stage IIIB, is described. The patient's course was characterized by an initial 15-months remission following radiation therapy. A relapse of Hodgkin's disease was treated with intensive chemotherapy. Thirteen months later the patient entered a rapid terminal course with multiple organ infiltrates and a leukemic peripheral blood. The leukemic phase was characterized by a 55,000 WGC with 48% immunoblasts, greater than 90% of which marked as T-cells. Although acute myelogenous leukemia, acute lymphocytic leukemia, lymphosarcoma cell leukemia and other tumors have been described in Hodgkin's disease after intensive therapy, this is the first report of the unusual association of a T-cell immunoblastic leukemia with Hodgkin's disease.

Antineoplastic Agents↗
PubMed1984

T-cell prolymphocytic leukemia with helper-cell phenotype and a review of the literature.

The majority of published cases of prolymphocytic leukemia (PLL) have been of B-cell origin. Nineteen cases of PLL of T-cell type have been described, as has a single case of PLL having a surface phenotype with features of both B-cells and T-cells. This report presents a review of these cases and comparison with one case of T-cell PLL. By using specific monoclonal antibody technique, this case was subcategorized into helper-cell phenotype: E-rosette(+), SIG(-), Anti-T(+), Anti-B(-), Anti-monocyte(-), OKT3(+), OKT4(+), OKT6(-), OKT8(-), Ia(+), and Tdt(-). Cytochemical studies showed paranuclear acid phosphatase granules. Postmortem examination revealed a predominant T-cell zone infiltration by the leukemic cells in the spleen and lymph nodes, with involvement of multiple organs. The application of the monoclonal antibody technique, which can be standardized among different laboratories to subclassify lymphoproliferative disorders into functional subtypes, should lead to a better understanding and more effective treatment of this disease.

Aged↗
PubMed1992

Splenectomy vs. alpha interferon: a randomized study in patients with previously untreated hairy cell leukemia.

Twenty patients with previously untreated hairy cell leukemia were randomized to undergo either splenectomy or to receive interferon alfa-N1, a highly purified natural alpha interferon, as primary therapy. A response in the peripheral blood elements to a hemoglobin greater than 110 gm/l, a granulocyte count greater than 1 x 10(9)/l, and a platelet count greater than 100 x 10(9)/l (Catovsky criteria) was noted in all ten patients receiving alpha interferon but in only three of the patients undergoing splenectomy (P = less than .01). Median time to response was longer in the ten interferon patients (153 days) than in the three splenectomy responders (20 days). Median time to treatment failure was significantly greater in the alpha interferon patients (greater than 18 months) than in the splenectomy patients (less than 1 month). Survival was no different since patients relapsing following splenectomy subsequently responded to alpha interferon. A significant decrease in leukemic bone marrow infiltration was observed in seven of ten patients receiving alpha interferon and in none of the patients undergoing splenectomy. Side effects, primarily infections, were more frequent in patients receiving interferon. Alpha interferon is preferable to splenectomy as initial treatment for hairy cell leukemia.

Adult↗
PubMed1978

Supplementary cytodiagnostic analyses of mononuclear cells of the cerebrospinal fluid using cytological markers.

Various methods of CSF cell differentiation are discussed. These methods provide additional information regarding the origin and, therefore, the types of pathological alterations occurring in the leptomeninges. They include the application of immunological and cytochemical markers to differentiate and identify B and T lymphocytes as well as cells from the monocyte-macrophage series and precursor cells of polymorphnuclear leukocytes. Application of these methods to CSF cells and the differentiation of CSF cells from 16 patients with inflammatory or neoplastic alterations were discussed. B cell or T cell type lymphocytes predominate with multiple sclerosis, T lymphocytes with tubercular meningitis. Varying quantities of B and T lymphocytes are found with viral meningitis. In one case the tumor cells of a reticulum cell sarcoma were identified in the CSF as T cells; in one case of plasmacytoma, tumor cells in the CSF were identified as B lymphocytes. In selected cases of leukemic or carcinomatous infiltration of the meninges and of medulloblastoma, CSF cells did not react to treatment with immunological markers.

B-Lymphocytes↗
PubMed1981

Congenital erythroleukemia. A case report.

The disease of a four week old boy is described, which presented with papulous skin infiltrations, lethargy, anemia and bilateral testicular swelling. The investigation of bone marrow, cerebrospinal fluid and skin biopsy revealed infiltration by a leukemic process which could be identified by means of cytology and cytochemistry as erythroleukemia at the stage of erythremic myelosis. Death occurred 20 days after the onset of symptoms. Only one previous report of congenital erythroleukemia could be found in the literature. The findings are briefly discussed.

Biopsy↗
PubMed2001

CLL cells in a brain metastasis of bronchial adenocarcinoma in a patient with three different neoplasms - case report.

OBJECTIVE: We report the case of a patient with three different malignancies who had a brain metastasis of bronchial adenocarcinoma with infiltrates of CLL lymphocytes and who had been operated for prostate cancer years before. - PATIENT AND RESULTS: A 72-year-old man was admitted to our department after a Jacksonian seizure. The MRI showed a left temporal mass lesion. The patient was suffering from chronic lymphocytic leukemia (CLL) for ten years, he had had surgery for prostate cancer eight years ago and the diagnosis of bronchial carcinoma was made during preoperative routine diagnostics. After neurosurgical intervention the histologic examination of the cerebral mass lesion disclosed metastasis of a PSA-negative adenocarcinoma with perivasal infiltrates of lymphocytic leukemic cells. - DISCUSSION: There are few reports about patients with three primary malignancies. CLL may play a role in enabling tumor cells to escape the immune response and could facilitate development of the prostate cancer and of a bronchial adenocarcinoma as secondary cancers in this patient. The combined occurrence of adenocarcinoma cells and CLL lymphocytes in the brain metastasis can be explained by impairment of the blood-brain-barrier in the carcinoma metastasis enabling extravasation of circulating leukemic cells.

Adenocarcinoma↗