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PubMed1993

Spontaneous remission of acute adult T-cell leukaemia with chromosomal abnormality infiltrating to skin and liver.

Acute type of adult T-cell leukaemia (ATL) has been recognized as highly-progressive T-cell malignancy with a median survival of 7 months. We present a case who had a spontaneous remission from acute type ATL with organ involvement and chromosomal abnormality implying very poor prognosis. Although the mechanism of spontaneous remission remains uncertain, our case was unique with regard to the progression and regression of leukaemia.

Chromosome Aberrations↗
PubMedDate not supplied

Imaging techniques in neoplastic meningiosis.

Since the introduction of CT and MRI as diagnostic aids, it has been possible to obtain direct images of neoplastic meningiosis. After more than ten years experience, the combination of MRI with the administration of a paramagnetic contrast medium is now accepted as the method of choice for the sensitive detection of meningeal diseases and for monitoring their treatment. The almost uniform character of leptomeningeal or pachymeningeal enhancement in the presence of infective, inflammatory, neoplastic, vascular or reactive changes is the reason for the restricted specificity of MRI, so that with the imaging process alone only very limited information about the etiology is available. Clinical data, laboratory findings, examination of the CSF and histopathological examination are therefore essential for interpreting the meningeal changes and making a differential diagnosis. Various pathophysiological processes can lead to a single meningeal enhancement visualizable with MRI: 1. a genuine disturbance of the blood-brain barrier is found in the presence of infection or inflammation, 2. leptomeningeal structures can be directly infiltrated by sheets or nodules of tumors, the blood vessels of which possess no intact blood-brain barrier, 3. physical or chemical irritants may produce of local inflammatory reaction with vascular proliferation and its corresponding enhancement, a 4. a pseudoenhancement may follow reactive dilatation of the vessels. In the present article the various appearances of neoplastic invasion of the meninges in MRI and their differential diagnosis will be described.

Brain Neoplasms↗
PubMed1993

Karyotype in multiple myeloma and plasma cell leukaemia.

Between October 1988 and October 1991, 104 patients with multiple myeloma and 6 with plasma cell leukaemia were studied cytogenetically. Abnormal karyotypes were found in bone marrow cells of 33 patients (30%). Most pathological karyotypes were complex with numerous modal and structural anomalies. Numerical anomalies most frequently involved chromosome 11 and structural aberrations occurred most often in chromosomes 1, 11 and 14. The most consistent structural aberration was a 14q+ chromosome (10 patients) resulting from a t(11;14)(q13;q32) in 4 patients and a t(8;14)(q24;q32) in 1 patient. Sequential cytogenetic studies were performed in 15 patients. In 5 of 8 cases with a normal karyotype at diagnosis, chromosomal anomalies were detected when disease progressed. In concomitant cytogenetic/cytological studies it was found that in the majority of patients with normal karyotype the mitoses originated from contaminating normal bone marrow cells. Pathological karyotypes were detected more frequently in pretreated than in untreated patients, in patients with plasma cell leukaemia than in patients with multiple myeloma, in patients with stage III and dense bone marrow infiltration than in patients with stage I. Patients with abnormal karyotype, irrespective if pretreated or not, had a significantly shorter median survival than those with normal karyotype. These findings suggest that karyotype is an independent prognostic factor in multiple myeloma.

Adult↗
PubMed1999

Specific cutaneous infiltrates in patients with myelogenous leukemia: a clinicopathologic study of 26 patients with assessment of diagnostic criteria.

BACKGROUND: Few recent studies have analyzed the clinicopathologic features of specific cutaneous manifestations of myelogenous leukemia in a large number of patients. OBJECTIVE: We characterize the clinical and histopathologic spectrum of specific cutaneous manifestations in acute (AML) and chronic (CML) myelogenous leukemia, ascertain further diagnostic criteria, and examine current prognosis. METHODS: Thirty-six lesions of specific cutaneous infiltrates from 26 patients with myelogenous leukemia (AML: 17 patients; M:F = 1:2.4; mean age: 52.6 years; AML-French-American-British [FAB] classification subtypes:M1 = 1, M2 = 3, M4 = 8, M5 = 5. CML = 9 patients; M:F = 4.5:1; mean age: 60.6 years) were retrospectively collected for the study. RESULTS: Cutaneous manifestations presented as solitary or multiple reddish to violaceous papules, plaques, and nodules (17 lesions), or as a generalized erythematous maculopapular eruption (9 lesions). Concurrent extramedullary involvement in other peripheral sites (eg, gums, pharynx, orbits) was observed in 10 patients. Histopathologically, lesions revealed nodular/diffuse infiltrates, often with perivascular and periadnexal accentuation, sparing of the upper papillary dermis, and prominent single arraying of neoplastic cells between collagen bundles. Extension to the subcutis was noted in all deep biopsy specimens (26 lesions). Cytomorphologically, medium to large-sized mononuclear cells (myeloblasts and atypical myelocytes) predominated in AML-M1 and M2, whereas M4 and M5 mainly showed small, medium-sized, or large mononuclear cells with slightly eosinophilic cytoplasm and indented, bi-lobular, or kidney-shaped nuclei (atypical monocytoid cells). In CML, either a variable mixture of mature and immature cells of the granulocytic series (myelocytes, metamyelocytes, eosinophilic metamyelocytes, and neutrophils) or a rather monomorphous infiltrate of mononuclear cells were found. Staining for naphthol AS-D chloroacetate-esterase (NASD) was positive in 24 of 36 lesions (66.6%; AML: 16; CML: 8). Immunohistochemical analysis on paraffin sections using a large panel of antibodies (16 lesions: AML: 13; CML: 3) showed strong reactivity for LCA (CD45), lysozyme, myeloperoxidase (MPD), LN2 (CD74), HLA-DR, and MT1 (CD43) in the majority of cases, and variable staining for monocyte/macrophage markers (KP1/CD68, PGM1/CD68, Mac387, Ki-M1p). The neuronal cell adhesion molecule (NCAM) marker CD56 was reactive in 2 cases of CML, but negative in all cases of AML. MIB1(Ki67) stained 20% to 80% of neoplastic cells. CD34, CD15, CD20, and CD3 were negative in all cases. No correlation between histochemical/immunohistochemical features with type of leukemia or FAB-subtype of AML was observed. All patients with CML and AML with adequate follow-up died within 24 months after onset of skin lesions (mean survival, AML: 7.6 months; CML: 9.4 months). CONCLUSION: Specific cutaneous lesions in AML and CML show distinctive clinicopathologic features that allow diagnosis in most cases. Immunohistochemistry on routinely fixed, paraffin-embedded tissue sections provides useful adjunctive information. Simultaneous expression of lysozyme, MPD, CD45, CD43, and CD74 militates in favor of a diagnosis of specific cutaneous infiltrate of myelogenous leukemia. Pitfalls in immunohistologic diagnosis mainly include lack of expression of some myeloid markers (lysozyme, MPD), and aberrant expression of T-cell markers (eg, CD45RO). Regardless of type of myelogenous leukemia, onset of specific skin manifestations correlates with an aggressive course and short survival.

Adult↗
PubMed2002

Matrix metalloproteinase-9 and vascular endothelial growth factor: a possible link in adult T-cell leukaemia cell invasion.

Plasma from a total of 57 patients with adult T-cell leukaemia (ATL) (acute ATL, 39 patients; lymphoma ATL, one patient; chronic ATL, 15 patients; smouldering ATL, two patients) and 20 healthy controls was analysed for the presence of type IV gelatinase activity with clinical features. A significant elevation of plasma matrix metalloproteinase-9 (MMP-9) was observed in some ATL patients, particularly in the patients with malignant cell infiltration. MMP-9 was found to be secreted into the conditioned medium from all ATL cell lines examined. Moreover, the corresponding mRNA was detectable both in all ATL cell lines examined and in the majority of primary acute ATL cells, indicating that ATL cells are capable of synthesizing and secreting MMP-9. We previously demonstrated that a high incidence of ATL cell infiltration was closely related to a high plasma level of vascular endothelial growth factor (VEGF) produced by ATL cells themselves. This present study showed that the presence of increased plasma MMP-9 was closely associated with elevated plasma VEGF in ATL patients. Furthermore, we showed that both increased plasma MMP-9 and VEGF were significantly related to high ATL cell infiltration. All these findings strongly suggest that MMP-9 and VEGF act co-operatively in the process of ATL cell invasion.

Acute Disease↗
PubMed2005

Clinicopathological features of cutaneous lesions of adult T-cell leukaemia/ lymphoma.

BACKGROUND: Adult T-cell leukaemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukaemia virus type I (HTLV-I). ATLL frequently involves the skin. OBJECTIVES: To correlate the clinicopathological features and prognosis in patients with ATLL and cutaneous lesions. METHODS: We examined the HTLV-I proviral state and the clinicopathological features of the cutaneous lesions in 80 patients with serum anti-ATL antibody, to clarify the correlation between macroscopic/histopathological findings and prognosis. Southern blot analysis was performed in all cases to detect monoclonal HTLV-I proviral DNA integration. RESULTS: The cutaneous lesions of 46 patients were positive for proviral DNA integration. The median survival time of patients with monoclonal proviral DNA integration in cutaneous lesions was 14 months, which was markedly shorter than that of patients negative for proviral DNA integration (72 months). Of the 46 patients with proviral DNA, 21 had solitary or multiple red nodules (including three with subcutaneous induration), eight had multiple red papules and 17 had erythema. Patients with papules and nodules had poorer prognosis than those with erythema. Histopathologically, the prognosis was poorer in patients with nodular or diffuse infiltration of medium-sized to large lymphoma cells, compared with those with perivascular infiltration of small to medium-sized lymphoma cells. CONCLUSIONS: Our results show a close correlation between clinicopathological features of HTLV-I-associated cutaneous lesions and prognosis.

Adult↗
PubMed2003

Patterns of bone marrow involvement in 58 patients presenting primary splenic marginal zone lymphoma with or without circulating villous lymphocytes.

We studied 86 bone marrow biopsies (BMB) from 58 patients presenting with primary splenic marginal zone lymphoma (PSMZL). In 42 patients, a splenectomy was performed which enabled a histopathological diagnosis. In these patients, 44 biopsies were carried out before, and 25 after, splenectomy. In 16 recently observed patients, 17 BMB led to PSMZL diagnosis, and these patients were treated without splenectomy. Seven different patterns of infiltrates were recognized: intravascular, interstitial, nodular, massive, plasmacytic mimicking myeloma and transformation into large B-cell lymphoma (DLBCL). The association of an intravascular infiltrate and nodules with a germinal centre and/or a marginal zone favoured a diagnosis of MZL. Immunohistochemistry demonstrated the expression of B cell-associated antigens and, in 40% of the patients, a monotypic lymphoplasmacytic cell component. These patients often presented a serum M component and autoimmune disorders. In the past, such cases have been diagnosed as lymphoplasmacytic lymphoma. BM involvement was present in all patients. Successive biopsies showed progression and, after chemotherapy, a slight decrease in infiltrates. Transformation into DLBCL occurred in 11 of 34 patients. The patterns described are not specific for PSMZL and occur also in primary nodal MZL and, more rarely, in MALT-type lymphoma.

Adult↗
PubMed2002

Skin infiltration with chronic lymphocytic leukemia is consistent with a good prognosis.

Skin infiltration with B-lymphocyte chronic lymphocytic leukemia (B-CLL) is rare. In contrast to Richters transformation of CLL or myeloid leukemias, skin involvement in CLL may be consistent with prolonged survival, as illustrated by the currently reported two cases. As in these patients, local therapy for skin disease may delay or obviate the need for systemic therapy in B-CLL.

Humans↗
PubMedDate not supplied

[Prostatic involvement in leukemia. Report of a case].

Infiltration of the prostate is frequent in the course of leukaemia. It is usually asymptomatic or may present in the form of classical bladder neck obstruction. The diagnosis is generally established during investigation of benign prostatic hypertrophy by biopsy or during treatment by resection. Treatment of leukaemia by systemic chemotherapy is unable to sterilize the prostatic site and must therefore be combined with local radiotherapy.

Aged↗
PubMed1999

Specific cutaneous lesions of the scalp in myelodysplastic syndrome with deletion of 20q.

We reported a specific skin lesion on the scalp in a patient with myelodysplastic syndrome (MDS), treated as refractory anemia with excess of blasts (RAEB). Histologically, a specimen from a nodule of the scalp consisted of a diffuse infiltration of atypical cells in the dermis and subcutaneous tissue. The patient died of acute leukemia 3 months later. Chromosomal examination of bone marrow cells revealed deletion of 20q and 21 trisomy. The specific cutaneous lesions in this patient were associated with acute transformation. The deletion of 20q and specific cutaneous lesions are regarded as signs of poor prognosis.

Biopsy, Needle↗
PubMed1993

Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death.

To delineate specific developmental roles of transforming growth factor beta 1 (TGF-beta 1) we have disrupted its cognate gene in mouse embryonic stem cells by homologous recombination to generate TGF-beta 1 null mice. These mice do not produce detectable amounts of either TGF-beta 1 RNA or protein. After normal growth for the first 2 weeks they develop a rapid wasting syndrome and die by 3-4 weeks of age. Pathological examination revealed an excessive inflammatory response with massive infiltration of lymphocytes and macrophages in many organs, but primarily in heart and lungs. Many lesions resembled those found in autoimmune disorders, graft-vs.-host disease, or certain viral diseases. This phenotype suggests a prominent role for TGF-beta 1 in homeostatic regulation of immune cell proliferation and extravasation into tissues.

Alleles↗
PubMed1993

Myelography, CT and MRI in leukaemic infiltration of the lumbar theca.

A 25-year-old woman with acute lymphoblastic leukaemia, while in remission, developed paraparesis, with faecal and urinary incontinence. CT demonstrated increased density of the lumbar theca and enlargement of the nerve roots. Myelography showed complete obstruction below the L3 level. MRI showed increased signal intensity in the lumbar sac on T1 weighting, and the cauda equina enhanced with gadolinium-DTPA. Lymphoblasts were seen in the lumbar spinal fluid. After chemotherapy, these abnormalities resolved, as did the paraparesis and incontinence.

Adult↗
PubMed2006

Spectrum of clinical presentation, treatment and prognosis in a series of eight patients with leukaemia cutis.

All types of leukaemia can disseminate to the skin, producing cutaneous deposits known as leukaemia cutis (LC). We undertook a retrospective study to review the clinical presentations, treatment and outcome of eight patients with LC managed in our department over a period of 12 years. The clinical phenotype varied, with erythematous papules and nodules occurring with greatest frequency. Infiltrated haemorrhagic plaques and perifollicular acneiform papules were also seen. Although patients were treated aggressively for their underlying leukaemia, and received therapy directed towards LC, they tended to be refractory to treatment and the diagnosis was generally associated with a poor prognosis. The exception was a patient with chronic lymphocytic leukaemia, who survived 3 years after developing LC.

Aged↗
PubMed2005

Characteristics of two mouse bcr-abl-transformed cell lines. II. Pathological lesions induced in mice.

Groups of six BALB/c mice each were intravenously inoculated with lethal doses of Ba-P210 (B210) or 12B1 cells and examined by autopsy, histology, special staining methods, enzyme histochemistry and immunohistochemistry. Clinical symptoms related to neoplasia consisted of a poor nutritional state, anaemia, mild to moderate dehydration and apathy. Paresis was apparent in three mice inoculated with 12B1 cells. Necropsy revealed splenomegaly in all animals. Sporadic haemorrhages in the lungs and enlargement of some lymph nodes were seen in some of the animals. Histological examination showed neoplastic cells in the spleen, in the bone marrow of the sternum, in the lung interstitium and in sinusoids of the liver in all mice. In six of nine brains examined, mild to moderate infiltration by neoplastic cells was observed. In all but two mice mild infiltration of the kidneys was found. The enlargement of lymph nodes was caused by an accumulation of neoplastic cells. The paresis was due to neoplastic infiltration of the vertebra, epidural space and spinal roots. Staining with Sudan black revealed cytoplasmic granules in neoplastic cells; however, the peroxidase reaction was negative. Numerous neoplastic cells disseminated in the red pulp of the spleen were reactive with CD3, CD79beta, CD11b and with neutrophil antibodies. We classified the disease induced by both of the cell lines as acute myeloid undifferentiated leukaemia (AML MO).

Acute Disease↗
PubMedDate not supplied

Differential diagnosis based on immunological-phenotyping in suspected malignant bone marrow involvement in childhood.

The diagnostic value of immunophenotyping (IP) as a first-line diagnostic method in diseases that infiltrate the childhood bone marrow (BM) or mimic infiltrated BM was examined. Two hundred and fifty unselected BM samples from 250 children suspected to have a malignancy infiltrating their BM were evaluated by means of IP and conventional morophological-cytochemical (MC) studies. We applied the alkaline phosphatase anti-alkaline phosphatase method for IP using a panel of monoclonal antibodies (Mabs) against leukocyte-associated antigens, neuroectodermal antigens, and intermediate filament antigens. Four cases of neuroblastoma, two cases of Ewing sarcoma, and one case of rhabdomyosarcoma were diagnosed by IP but not by MC studies. In nine cases of acute leukemia bone marrow blasts could not be ascribed to a specific lineage on the basis of blast morphology or histochemistry. Eight samples without morphological evidence of malignant infiltration revealed an increased percentage of immature B cell precursors (CD10+, TdT+) suggesting acute lymphoblastic leukemia. None of these children has developed malignant lymphoproliferative disease. Our data suggest that the immunological evaluation of BM in childhood is highly capable of discriminating between different malignant populations but it does not recognize malignancy and therefore supplements but cannot replace conventional methods for diagnosis.

Adolescent↗
PubMed2006

Selective COX-2 inhibitor celecoxib prevents experimental autoimmune encephalomyelitis through COX-2-independent pathway.

Cyclooxygenase (COX) is a key enzyme of arachidonic acid metabolism and exists as two distinct isoforms. COX-1 is constitutively expressed in most tissues, whereas COX-2 is inducibly expressed at the site of inflammation. Selective inhibitors of COX-2 have been developed and have been used as anti-inflammatory agents. Here, we show that a new-generation COX-2 inhibitor, celecoxib, inhibited experimental autoimmune encephalomyelitis (EAE). Celecoxib, but not other COX-2 inhibitors such as nimesulid, prevented myelin oligodendrocyte glycoprotein (MOG) induced EAE when administrated orally on the day of disease induction. Moreover, celecoxib inhibited EAE in COX-2-deficient mice, indicating that celecoxib inhibited EAE in a COX-2-independent manner. In celecoxib-treated mice, interferon-gamma (IFN-gamma) production from MOG-specific T cells was reduced and MOG-specific IgG1 was elevated compared with vehicle-treated mice. Infiltration of inflammatory cells into the central nervous system and the expression of adhesion molecules, P-selectin and intercellular adhesion molecule-1 (ICAM-1), and a chemokine, monocyte chemoattractant peptide-1 (MCP-1), were inhibited when mice were treated with celecoxib. These results suggest that celecoxib may be useful as a new additional therapeutic agent for multiple sclerosis.

Animals↗
PubMed2006

Morphological and functional determinants of fluoxetine (Prozac)-induced pulmonary disease in an experimental model.

Fluoxetine treatment effects were determined by evaluating respiratory mechanics (elastance/resistance) and exhaled nitric oxide, as well as mononuclear and polymorphonuclear cell recruitment into the lungs, in an experimental guinea pig model. Guinea pigs were divided into four groups: Fl (fluoxetine only, n=7); Fl+Sw (fluoxetine and forced swimming, n=7); Ns+Sw (normal saline and forced swimming, n=8); and Ns (normal saline only, n=8). Treated animals received oral fluoxetine (10 mg/(kg day)) for 30 consecutive days. On day 31, all animals were anesthetized and mechanically ventilated so that respiratory system elastance and resistance, as well exhaled nitric oxide, could be determined. The lungs were then excised en bloc for histological and immunohistochemical evaluation. Forced swimming induced bronchodilation in untreated animals and bronchoconstriction in fluoxetine-treated animals. Fluoxetine treatment was also associated with mononuclear infiltration (predominantly into alveolar walls) and neutrophil recruitment. In addition, levels of exhaled nitric oxide, an inflammatory marker, were higher in fluoxetine-treated animals. Swimming-induced stress also amplified mononuclear cell recruitment to the lungs. These results show that, in this experimental model, fluoxetine treatment reproduces the pathology of chronic interstitial pneumonia in humans.

Airway Resistance↗
PubMed2000

Successful allogeneic bone marrow transplantation in a case of adult precursor B-lymphoblastic lymphoma.

A 42-year-old woman was admitted to the National Cancer Center Hospital in Tokyo, Japan, because of lumbago and bilateral leg pain. Clinical examination revealed a retroperitoneal bulky tumor, a breast tumor, and lymphoblasts in bone marrow. She did not have surface lymph node swelling or systemic symptoms such as weight loss and night sweats. Lymphoblasts in bone marrow were positive for CD10 and CD19 but negative for CD20, surface immunoglobulin, and T-cell antigens. Needle biopsy of a retroperitoneal mass revealed diffuse infiltration of lymphoblastic tumor cells. Because the cells were immunoreactive for CD79a, CD10, and terminal deoxynucleotidyl transferase, the patient was diagnosed as having precursor B-lymphoblastic lymphoma (which is rare in adults) with bone marrow involvement. The patient achieved complete remission by an induction therapy for acute lymphoblastic leukemia, underwent allogeneic bone marrow transplantation, and has remained in complete remission for more than 3 years.

Adult↗