Molecular detection of acute lymphoblastic leukaemia in boys with testicular relapse.
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AIMS: To determine the role of polymerase chain reaction (PCR) based minimal residual disease (MRD) detection of leukaemia specific DNA in testicular relapse in childhood acute lymphoblastic leukaemia. METHODS: DNA was obtained from archival testicular and bone marrow samples from boys with acute lymphoblastic leukaemia who relapsed in the testes. Overlapping DJH clone specific primers derived from clonal immunoglobulin heavy chain (IgH) gene rearrangement in each case were used to analyse testicular or bone marrow DNA. RESULTS: Histologically normal end of treatment testicular biopsies in the five patients in longterm remission were all MRD negative, but MRD positive in three of six boys with subsequent testicular relapse. Histologically normal bone marrow samples taken at the end of treatment were MRD negative in five of seven cases, but MRD positive in all cases at the time of isolated testicular relapse. Three boys with unilateral testicular relapse underwent unilateral orchidectomy, rather than bilateral testicular irradiation, as part of their treatment. Two of these boys were MRD positive in the histologically uninvolved testes, and both had subsequent relapses either in the testes or the bone marrow, while the MRD negative patient has not had a testicular relapse. CONCLUSIONS: The presence of MRD in testicular tissue can be assayed with a PCR based method to detect clone specific antigen receptor gene rearrangements. In this setting, PCR is more sensitive than conventional testicular histology for predicting clinical outcomes. MRD assays might be useful in the management of boys at the time of isolated testicular relapse, to confirm the presence of unilateral testicular disease. (+info)
Ultrasound imaging of apoptosis: high-resolution non-invasive monitoring of programmed cell death in vitro, in situ and in vivo.
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A new non-invasive method for monitoring apoptosis has been developed using high frequency (40 MHz) ultrasound imaging. Conventional ultrasound backscatter imaging techniques were used to observe apoptosis occurring in response to anticancer agents in cells in vitro, in tissues ex vivo and in live animals. The mechanism behind this ultrasonic detection was identified experimentally to be the subcellular nuclear changes, condensation followed by fragmentation, that cells undergo during apoptosis. These changes dramatically increase the high frequency ultrasound scattering efficiency of apoptotic cells over normal cells (25- to 50-fold change in intensity). The result is that areas of tissue undergoing apoptosis become much brighter in comparison to surrounding viable tissues. The results provide a framework for the possibility of using high frequency ultrasound imaging in the future to non-invasively monitor the effects of chemotherapeutic agents and other anticancer treatments in experimental animal systems and in patients. (+info)
Fine-needle aspiration of secondary neoplasms involving the salivary glands. A report of 36 cases.
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Metastases or secondary deposits account for 16% of the malignant neoplasms involving the major salivary glands. A correct diagnosis of a secondary neoplasm is important to avoid unnecessary radical surgery and to guide further therapy. Fine-needle aspiration biopsy (FNAB) is an excellent noninvasive diagnostic tool for evaluating salivary gland lesions. We reviewed 36 secondary malignant salivary gland neoplasms evaluated by FNAB. Ancillary studies were performed in selected cases. Follow-up included clinical correlation and review of histologic material. For 4 adenocarcinomas, 4 squamous cell carcinomas, 1 undifferentiated carcinoma, 1 cutaneous basal cell carcinoma, 10 cutaneous melanomas including 1 desmoplastic variant, 3 osteosarcomas, 11 non-Hodgkin lymphomas, and 2 multiple myelomas, there was 1 false-negative FNAB result. The desmoplastic melanoma was interpreted as reactive lymphoid hyperplasia. A malignant diagnosis was given in all remaining cases except the secondary basal cell carcinoma, which was diagnosed as a neoplasm with basal cell features. FNAB is a reliable tool to differentiate hematologic malignant neoplasms and melanomas from other salivary gland neoplasms. A complete knowledge of the clinical history, review of previous pathologic materials, and, in some instances, the use of ancillary studies are crucial for recognizing solid malignant neoplasms secondarily involving the salivary glands. (+info)
Immunophenotyping of acute lymphoblastic leukaemia in routinely processed bone marrow biopsy specimens.
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AIMS: To assess the value of immunophenotyping of acute lymphoblastic leukaemia (ALL) in routinely processed bone marrow trephine biopsy specimens and to establish a minimum panel of antibodies to assess lymphoid lineage and enable differentiation from acute myeloid leukaemia. METHODS: 45 routinely processed bone marrow biopsy specimens (formalin fixed, paraffin embedded and mildly decalcified in EDTA) reported to contain leukaemic infiltrates on the basis of cytomorphological and enzyme-cytochemical analysis of bone marrow smears (22 c-ALL, 11 T-ALL, 2 B-ALL, 10 u-ALL (unclassified)) were immunostained by the ABC method with a broad panel of 26 antibodies against various haemopoietic antigens. RESULTS: Staining with antibodies directed against myeloperoxidase and lysozyme showed that seven cases were either biphenotypic or mixed leukaemias (2), or of myelogenous origin (acute myeloid leukaemia (AML)-M1 (2); AML-M4 (2); AML-M5a (1)). Five of these seven cases had been diagnosed initially as u-ALL. Three further cases with no compact leukaemic infiltrates were excluded. ALL was confirmed in the remaining 35 cases. Because of revised diagnoses, the total numbers of ALL subtypes changed (23 c-ALL, 8 T-ALL, 2 B-ALL, 2 u-ALL). Immunostaining of more than 10% of blast cells in at least one case was found with 19 of the 26 antibodies. The most sensitive lineage specific antibodies for diagnosis were found to be anti-CD10 for c-ALL (22/23) and beta F1 for T-ALL (6/8). Expression of aberrant antigens was fairly common--for example, 7/23 cases of c-ALL stained with antibodies against T cell associated antigens. CONCLUSIONS: Immunohistochemical investigation of routinely processed bone marrow biopsy specimens enables reliable detection of ALL subtypes c-ALL and T-ALL. A minimum panel of antibodies, against TdT, CD34, myeloperoxidase, lysozyme, CD10, CD79a, and CD20, and the antibody beta F1, is proposed for the immunophenotyping of acute leukaemia. (+info)
A new cause of 'non-responsiveness' in coeliac disease?
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A 42 year old man presented with gluten-responsive coeliac disease and secondary pancreatic insufficiency. Subsequently his symptoms relapsed and repeat small intestinal biopsy showed villous atrophy and infiltration by leukaemic cells, despite continuation of a gluten-free diet. Serious causes of relapse and non-responsiveness in coeliac disease include enteropathy-associated T-cell lymphoma, ulcerative jejunitis and an end-stage hypoplastic mucosa. This is the first report of non-responsiveness due to infiltration by leukaemia. (+info)
Gi and Gq/11 proteins are involved in dissemination of myeloid leukemia cells to the liver and spleen, whereas bone marrow colonization involves Gq/11 but not Gi.
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The migration of leukocytes into tissues is regulated by chemokines and other chemotactic factors that act on receptors that signal through Gi proteins. It seems likely that the colonization of tissues during dissemination of hematopoietic tumor cells is similarly regulated. In fact, dissemination of a T-cell hybridoma, a model for T lymphoma, was blocked when Gi proteins were inactivated by the S1 catalytic subunit of pertussis toxin that had been transfected into those cells. Pertussis toxin S1 blocked dissemination of MDAY-D2 murine myeloid leukemia cells to the liver and spleen, as in T-cell hybridoma cells, but it did not prevent bone marrow colonization. In contrast, overexpression of a function-defective mutant of the Gq/11 protein blocked dissemination to the bone marrow and also prevented Gq/11 dissemination to the liver and spleen. This indicates that the influx of these myeloid cells into all tissues requires the Gq/11 protein in addition to the Gi protein in the liver and spleen. (Blood. 2000;96:691-698) (+info)
Cutaneous promyelocytic sarcoma at sites of vascular access and marrow aspiration. A characteristic localization of chloromas in acute promyelocytic leukemia?
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Extramedullary disease (EMD) is a rare clinical event in acute promyelocytic leukemia (APL). Although the skin is involved in half of the reported EMD cases, the occurrence of cutaneous promyelocytic sarcoma (PS) has been described very rarely. We report here three cases of PS which have the peculiarity of appearing at sites of punctures for arterial and venous blood and marrow samples (sternal manubrium, antecubital fossa, wrist over the radial artery pulse, catheter insertion scar). At presentation, all patients had hyperleukocytosis and a morphologic diagnosis of microgranular acute promyelocytic leukemia variant confirmed at the genetic level by demonstration of the specific chromosomal translocation t(15;17). A BCR3 type PML/RARa transcript was documented in the two patients for whom diagnostic RT-PCR was available. Patients had morphologic bone marrow remission at the time the PS appeared. A predilection for the development of cutaneous PS at sites of previous vascular damage has been noted, but the pathogenesis remains largely unknown. A potential role for all-trans retinoic acid has been advocated, although one of the three patients in our series had received no ATRA. A review of the literature revealed six similar cases and hyperleukocytosis at diagnosis was a consistent finding in all of them. A careful physical examination of these particular sites in the follow-up of patients at risk, as well as cutaneous biopsy and laboratory examination of suspected lesions are strongly recommended. (+info)
Clonotypic polymerase chain reaction confirms minimal residual disease in CLL nodular PR: results from a sequential treatment CLL protocol.
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Patient-tumor-specific oligonucleotides were generated for the detection of minimal residual disease (MRD) in a highly specific and sensitive clonotypic polymerase chain reaction (cPCR). The clone-specific region of highest diversity, CDR-III, was PCR amplified and sequenced. Nested CDR-III clonotypic primers were used in a semi-nested cPCR with a sensitivity of at least 1 in 10(5) cells. Patients with protocol-eligible Rai intermediate or high-risk chronic lymphocytic leukemia (CLL) received induction with fludarabine 25 mg/m(2) per day for 5 days every 4 weeks for 6 cycles, followed by consolidative high-dose cyclophosphamide (1.5, 2.25, or 3g/m(2)). cPCR was performed on peripheral blood and bone marrow mononuclear cells. All 5 patients achieving a clinical partial remission (PR) studied by cPCR were positive. Five patients achieved nodular PR (nPR) (residual nodules or suspicious lymphocytic infiltrates in a bone marrow biopsy as the sole suggestion of residual disease). Five of 5 patients with nPR were cPCR positive. In contrast, flow cytometry for CD5-CD19 dual staining and kappa--lambda clonal excess detected MRD in only 3 of the same 5 nPR patients, all of whom were cPCR positive, and immunohistochemistry detected MRD in only 1 of 4 assessable patients. Three of 7 CR patients evaluable by cPCR had MRD. Only 1 CR patient had MRD by flow cytometry; that patient was also cPCR positive. These data support the conclusions that nodular PR in CLL represents MRD and that clonotypic PCR detects MRD in CLL more frequently than flow cytometry or immunohistochemistry. (Blood. 2001;97:1929-1936) (+info)