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PubMed2003

Leukaemic pulmonary infiltrates in adult acute myeloid leukaemia: a high-resolution computerized tomography study.

Leukaemic infiltration of the lungs may occur in acute myeloid leukaemia (AML). Pulmonary infiltrates are usually microscopic and invariably associated with hyperleucocytosis. Four AML patients with respiratory symptoms and low leucocyte counts underwent standard chest radiography, bronchoscopy with bronchoalveolar lavage and high-resolution computerized tomography (HRCT) of the lungs. HRCT scans showed pulmonary infiltrates with alveolar, interstitial, mixed and peribronchial/perivascular patterns in all patients, including one with negative standard radiographic findings. Infectious agents were excluded. Histology of the lung biopsy/autopsy specimens showed leukaemic infiltrates. Pulmonary leukaemia may be the cause of pulmonary infiltrates, even in non-hyperleucocytosic AML patients with low blast counts.

Acute Disease↗
PubMed1993

Urticaria-pigmentosa-like lesions in acute lymphoblastic leukaemia (2 cases).

Two males aged 12 and 38 years presented with widespread severely pruritic blackish spots for 15 days. Widespread slate-grey patches and erythematous hyperpigmented plaques were observed with a positive Darier's sign. There were associated neck swellings, abdominal pain, anorexia, weight loss and bleeding gums in both. Peripheral blood and bone marrow showed blast cells, anaemia and thrombocytopenia. Cell surface markers confirmed the presence of acute lymphoblastic leukaemia. Skin biopsy showed an infiltrate of lymphoblasts as well as mast cells. Partial response was noted with cytotoxic therapy in 1 patient. Thus lesions mimicking urticaria pigmentosa may be the presenting sign of acute lymphoblastic leukaemia.

Adult↗
PubMed1996

[Histo-morphometry of bone mass and cellularity using image analysis: characterization of infiltration patterns in CLL].

PURPOSE: The aim of this study was to investigate a possible influence of lymphocytic infiltration in Chronic Lymphocytic Leukemia (CLL) on bone mass, according to the infiltration patterns. MATERIAL AND METHODS: We have studied histological preparations from decalcified and paraffin included bone biopsies and used a histomorphometric study through a mixed (interactive-automatic) image analysis, in order to quantify bone trabecular (BT/TV) and cellular volume (CV). Preparations were visualized via a 2.5 objective; a video camera was adapted and connected to a computer with analogical-digital converter incorporated. After the image was captured, a binarization was made by trabecular and medullary spaces segmentation; automatically, we calculated trabecular area (TA) and cellular area (CA). Expressions indicated above were used to calculate BV/TV and CV, expressed in percentage: BV/TV (%) = [TA/(TA + CA)] x 100, and CV (%) = [CA/(TA + CA)] x 100. RESULTS: 92 normal biopsies and 79 CLL biopsies were studied (Nodular 12, Diffuse 22, Interstitial 23, Mixed 22). BT/TV in normal subjects age over 45, was 18.40%; it was lower in CLL subjects, 17.25%. CV was 33.62% in normal cases and significantly higher in CLL with 42.95%. According to the infiltration patterns, Nodular pattern showed similar value to normal biopsies, versus Diffuse pattern with BT/TV of 16.19% and CV of 51.49%. Significantly, a high CV value was accompanied of a low B/TV value, in normal and CLL subjects. CONCLUSIONS: We analyzed histomorphometrically trabecular volume as expression of bone mass in undecalcified biopsies. CLL infiltration tended to show a lower trabecular volume. Diffuse pattern presented the higher cellular infiltration and bone mass destruction.

Aged↗
PubMed2001

[Angiogenesis in patients with hematologic malignancies].

Angiogenesis in Patients with Hematologic Malignancies The importance of angiogenesis for the progressive growth and viability of solid tumors is well established. Emerging data suggest an involvement of angiogenesis in the pathophysiology of hematologic malignancies as well. Recently, we and others have reported increased angiogenesis in the bone marrow of patients with acute myeloid leukemia (AML) and normalization of bone marrow microvessel density when patients achieved a complete remission (CR) after induction chemotherapy. Tumor angiogenesis depends on the expression of specific mediators that initiate a cascade of events leading to the formation of new microvessels. Among these, VEGF (vascular endothelial growth factor), FGF (fibroblast growth factor) and angiopoietins play a pivotal role in the induction of neovascularization in solid tumors. These cytokines stimulate migration and proliferation of endothelial cells and induce angiogenesis in vivo. Recent data suggest an important role for these mediators in hematologic malignancies as well. Isolated AML blasts overexpress VEGF and VEGF receptor 2. Thus, the VEGF/VEGFR-2 pathway can promote the growth of leukemic blasts in an autocrine and paracrine manner. Therefore, neovascularization and angiogenic mediators/receptors may be promising targets for anti-angiogenic and anti-leukemic treatment strategies. The immunomodulatory drug thalidomide inhibits angiogenesis in animal models. Moreover, it has significant activity in refractory multiple myeloma. In a current phase II study for patients with primary refractory or relapsed multiple myeloma using a combination of thalidomide with hyperfractionated cyclophosphamide and dexamethasone (Hyper-CDT), we observed a partial remission in 12 of 14 evaluable patients (86%). Thus, this combination seems to be very potent. Furthermore, we evaluated the safety and efficacy of thalidomide in patients with AML not qualifying for intensive cytotoxic chemotherapy. 20 patients aged 58-85 (median 69) years were recruited to this phase I/II study and were treated with a dose of 200-400 mg per os daily for a duration of 1-40 (median 6) weeks, dependent on the individual tolerability of the drug. In 4 patients we observed a partial response (PR - defined as more than 50% reduction in leukemic blast infiltration in the bone marrow). This was accompanied by an increase in platelet counts and hemoglobin values. One additional patient showed a significant improvement of peripheral blood counts without fulfilling the criteria of a PR. In parallel, we observed a significant decrease in microvessel density in these 5 patients during treatment with thalidomide. In conclusion, thalidomide seems to have anti-angiogenic as well as anti-leukemic activity in AML. The VEGF/VEGFR-2 pathway seems to play an important role in AML. Therefore, receptor tyrosine kinase inhibitors like SU5416 or SU6668 are currently evaluated in the context of phase II studies in AML. We could recently induce a stable remission in a patient with second relapse of her AML refractory towards chemotherapy by administration of SU5416 (compassionate use), a tyrosine kinase inhibitor of VEGFR-2 and ckit. Current and future studies will clarify the role of anti-angiogenic treatment strategies in AML and other hematologic malignancies.

Aged↗
PubMedDate not supplied

Disseminated necrotizing leukoencephalopathy following irradiation and methotrexate therapy for central nervous system infiltration of leukemia and lymphoma.

The authors report four adult patients with disseminated necrotizing leukoencephalopathy (DNL) following therapy for central nervous system (CNS) involvements of leukemia and lymphoma. Five to fourteen months after starting therapy with 30.6-62.5 Gy of whole brain irradiation and 120-500 mg of intrathecal methotrexate (MTX), DNL developed. Brain CT scans demonstrated a characteristic symmetrical white matter low density area. Furthermore, the brain CT scans disclosed tumorous lesions with contrast enhancement in three cases. In two of the three cases autopsy proved the tumorous lesions to be necrotic foci but not leukemic tumors. Post-mortem neuropathological studies of three patients disclosed characteristic features of DNL: multiple coagulative necrosis in the white matter with myelin degeneration, swollen axons, prominent calcification, and enlarged reactive astrocytes. Three of the four patients obviously received greater doses of whole brain irradiation and intrathecal MTX than patients who remained free from DNL after treatment with whole brain irradiation and/or MTX. Analysis of the etiological factors in this series underscores the prevailing danger of treatment for neoplastic CNS involvement with excessive doses of whole brain irradiation combined with intrathecal MTX.

Adolescent↗
PubMed2005

Precursor B-cell lymphoblastic leukemia as a cause of a bilateral nephromegaly.

Nephromegaly and non-oliguric acute renal failure is an unusual manifestation of lymphoblastic infiltration of the kidneys. We report the clinical history of a female child where a precursor B-cell lymphoblastic proliferation was diagnosed at the age of 21 months by a surgical renal biopsy for an unexplained bilateral nephromegaly. Lymphoblastic infiltration should be suspected in any patient presenting with unexplained renal failure and enlarged kidneys. The importance of renal biopsy to identify the etiology of renal failure and nephromegaly is emphasized.

Acute Kidney Injury↗
PubMed2006

Torsion of the testicular appendix: importance of associated acute inflammation.

BACKGROUND: Torsion of the testicular appendix is the commonest cause of acute scrotum in children. The histological picture of these cases is variable and many show a heavy acute inflammatory cell infiltrate, unlike the response to pure ischaemic necrosis in other organs. The clinical implications and consequences of this associated inflammation are not clear. METHODS: A retrospective review of all cases presenting with torsion of the testicular appendix between 1987 and 2005 was carried out. In all, 79 cases were reviewed and the degree of acute inflammatory cell infiltrate and other morphological parameters were assessed and compared with the patients' clinical, operative and postoperative findings. Stains for bacteria and fungi were examined. RESULTS: A positive correlation was found between the severity of acute inflammatory cell infiltrates and the longer duration of symptoms and presence of clinical evidence of torsion of the testicular appendages. No other association was detected between the pattern or degree of acute inflammatory cell infiltrate and any other clinicopathological variable that may indicate pyogenic infection. No bacteria or fungal elements were identified. Marked lymphatic dilation may be the only histological finding to indicate the presence of early torsion in cases of scrotal pain secondary to torsion of the appendix testis. CONCLUSION: Heavy acute inflammatory cell infiltrates in the torted testicular appendix can be regarded as marker of progression of this condition. Investigation for infection is therefore not necessary in such cases.

Acute Disease↗
PubMed1994

HTLV-I proviral DNA amount correlates with infiltrating CD4+ lymphocytes in the spinal cord from patients with HTLV-I-associated myelopathy.

A quantitative method utilizing polymerase chain reaction was employed to evaluate the amount of human T-cell leukemia virus type I (HTLV-I) proviral DNA in the affected spinal cords from patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Central nervous system (CNS) tissues were obtained at post-mortem from five patients with HAM/TSP, who vary in the duration of illness from 2.5-10 years, and one patient with adult T-cell leukemia (ATL), who had leukemic cell infiltration in the CNS. The presence of HTLV-I pX and pol sequences in the CNS tissues were demonstrated in all patients examined. In HAM/TSP, the proviral DNA quantified in the thoracic cord was 0.002-2 copies per 100 tissue cells, and that in the peripheral blood mononuclear cells (PBMC) was 2-8 copies per 100 PBMC. The proviral DNA amount in the thoracic cord of the patient with ATL was 0.4 copies per 100 tissue cells. An apparent propensity for the amount of integrated HTLV-I in the thoracic cord to decrease with the disease duration in patients with HAM/TSP was observed. The decline in HTLV-I proviral DNA amount in the thoracic cord lesions was paralleled with the alteration of proportion of CD4+ T lymphocytes in patients with HAM/TSP. These findings suggest that preferential virus reservoir may be infiltrating CD4+ T lymphocytes in the spinal cord lesions of patients with HAM/TSP, and HTLV-I infection in the CNS of patients is declining with the disease duration in spite of the chronic course of neurological manifestations at least in some patients with HAM/TSP.

Aged↗
PubMed2004

Acute myeloid leukemia presenting as bilateral proptosis from diffuse extraocular muscle infiltration.

PURPOSE: To report a case of acute myeloid leukemia with bilateral proptosis as the sole presenting sign. DESIGN: Observational case report. METHODS: A patient with bilateral proptosis was seen in consultation by pediatric ophthalmology. RESULTS: Complete blood count, computerized tomography, and bone marrow biopsy confirmed the diagnosis of acute myeloid leukemia, with the proptosis due to diffuse infiltration of all extraocular muscles. CONCLUSION: In a child with the sudden onset of proptosis without any other systemic findings, the diagnosis of acute leukemia must be considered.

Acute Disease↗
PubMed2003

Retinoic acid syndrome: manifestations, pathogenesis, and treatment.

All-trans retinoic acid (ATRA) is a potent differentiation agent that is effective therapy in acute promyelocytic leukaemia. Although ATRA is generally well tolerated, some patients develop retinoic acid syndrome. This syndrome is manifested by unexplained fever, weight gain, respiratory distress, interstitial pulmonary infiltrates, pleural and pericardial effusion, episodic hypotension, and acute renal failure. However, if identified early enough, effective therapy can be administered. This chapter discusses the clinical aspects and pathogenesis of retinoic acid syndrome.

Chemotaxis, Leukocyte↗
PubMed1996

[Clinical significance of soluble interleukin-2 receptor levels in the cerebrospinal fluid in patients with adult T-cell leukemia complicated with meningeal infiltration].

We measured soluble interleukin-2 receptor (sIL-2R) levels in the cerebrospinal fluid (CSF) of patients with hematological malignancies especially, adult T-cell leukemia (ATL) and non-Hodgkin's lymphoma (NHL) with or without meningeal infiltration. CSF levels of sIL-2R were significantly higher in patients with ATL and NHL with meningeal infiltration than in patients with both diseases without meningeal infiltration. The sIL-2R levels in CSF were elevated in 4/4 ATL patients (100%) and 3/13 NHL patients (23%) with meningeal infiltration. CSF levels of sIL-2R from ATL patients with meningeal infiltration had a tendency to elevate in correlation with numbers of mononuclear cells and lactic dehydrogenase (LDH) in CSF. However, these had no correlation with serum levels of sIL-2R. Therefore, sIL-2 levels in CSF may be useful in the diagnosis of meningeal infiltration in patients with ATL, are probably specific markers for meningeal infiltration of ATL.

Adolescent↗
PubMed1998

Transrectal ultrasound appearance of hematolymphoid malignancies involving the prostate.

OBJECTIVES: Although the clinical presentation and physical examination findings in patients with lymphoma or leukemia involving the prostate have been described previously, the transrectal ultrasound appearance of hematolymphoid malignancies involving the prostate has not been previously described. METHODS: Nine patients with prostate cancer diagnosed by transrectal ultrasound-guided prostate biopsies were found to have hematolymphoid malignancies involving the prostate at the time of subsequent radical prostatectomy and pelvic lymph node dissection. The ultrasound images and prostate needle biopsy results are presented. RESULTS: Prospective analysis of transrectal ultrasound images revealed no abnormality other than hypoechogenicity typical of prostate cancer in 7 of the 9 patients (77.8%). In 2 patients, the ultrasound images were free of any abnormalities. In 2 of the 9 patients (22.2%), the prostate needle biopsies demonstrated suspicious lymphocytic infiltrate in addition to prostate cancer. CONCLUSIONS: Transrectal ultrasound does not detect hematolymphoid malignancies involving the prostate. Ultrasound-guided biopsies of the prostate have a very low rate of detecting these malignancies.

Adenocarcinoma↗
PubMed1995

Infiltrate of chronic lymphocytic leukemia appearing as a periapical radiolucent lesion.

This report presents a case of a mandibular premolar with a vital pulp and a periapical radiolucent lesion in a patient with a history of chronic lymphocytic leukemia. Biopsy of the lesion revealed an infiltrate of chronic lymphocytic leukemia in the mandible, which is quite rare. This lesion may have portended a worsening of the patient's condition and downgrading of her prognosis.

Aged↗
PubMed1996

Ocular manifestations of leukaemia in Ethiopians.

A prospective ophthalmic evaluation of 74 newly diagnosed and 34 old (on follow-up) leukaemic patients, carried out from March 1990 to December 1995 is described. Primary ocular involvement, that is leukaemic retinal infiltrates, were detected in 32% of the newly diagnosed. In contrast, none of the old leukaemic patients had this lesion. In 69% of the new and 21% of the old cases, secondary ocular manifestations of leukaemia were observed. The major secondary ocular manifestation of leukaemia in both groups was intra-retinal haemorrhage. A variety of miscellaneous ocular findings, such as cataract, pterygium, pingeculae, etc. were detected in 36% of all leukemics. These findings indicate the importance of a complete ophthalmologic evaluation in the diagnosis, follow-up and management of leukaemic patients.

Adolescent↗
PubMed1994

Acute neutrophilic dermatosis with myeloblastic infiltrate in a leukemia patient receiving all-trans-retinoic acid therapy.

We report a case of leukemia-associated acute febrile neutrophilic dermatosis (Sweet's syndrome) that is unique because its initial histologic findings mimicked leukemia cutis. Otherwise, the clinical manifestations and response to corticosteroid therapy were typical of Sweet's syndrome. The onset of the dermatosis coincided with the onset of neutrophilic differentiation induced by single-agent leukemia therapy with all-trans-retinoic acid (ATRA). Subsequent exacerbation of the manifestations of Sweet's syndrome and the ultimate conversion of the histologic picture to the expected mature neutrophilic dermal infiltrate coincided with the completion of neutrophilic differentiation in the peripheral blood and bone marrow. The ability of immature neutrophil precursors to induce cutaneous lesions of Sweet's syndrome may indicate an ATRA-induced functional maturation that slightly precedes its effect on morphologic maturation. We conclude that a cutaneous infiltrate of early neutrophil precursors does not preclude a diagnosis of Sweet's syndrome in patients with acute leukemia who respond to ATRA therapy.

Diagnosis, Differential↗
PubMed1998

A prospective study of ocular manifestations in childhood acute leukaemia.

PURPOSE: To determine the prevalence of ocular manifestations in childhood acute leukaemia at the time of presentation. METHODS: Eighty-two children with acute leukaemia were examined for ocular lesions within two days of diagnosis before starting chemotherapy. The detailed ocular examination of both eyes was carried out by the ophthalmologist irrespective of the presence or absence of eye symptoms in all cases. RESULTS: Only 3 out of 82 children presented with eye symptoms (3.6%). However, ocular changes were found in 14 children (17%); ten with lymphoblastic and four with myeloid leukaemia. The ocular lesions observed were proptosis, intraretinal haemorrhages, white centered haemorrhages, cotton wool spots, macular haemorrhage, subhyaloid haemorrhage, vitreous haemorrhage, papilloedema, cortical blindness, sixth nerve palsy, and exudative retinal detachment with choroidal infiltration. CONCLUSION: In view of the high prevalence of asymptomatic ocular lesions in childhood acute leukaemia, routine ophthalmic examination should be included as a part of evaluation at the time of diagnosis.

Child↗
PubMed2002

Significance of the levels of bone marrow lymphoid infiltrate in chronic lymphocytic leukemia patients with nodular partial remission.

Patients with chronic lymphocytic leukemia (CLL) are considered in nodular partial remission (nPR) when they are in remission but bone marrow biopsies show rare nodules. The significance of the level of residual disease in nPR is not known. We studied 91 previously untreated CLL patients who were treated with fludarabine alone, fludarabine with prednisone, or fludarabine with cyclophosphamide and achieved nPR at the end of six courses. We compared bone marrow lymphoid infiltration before therapy and at the end of three and six courses of therapy as evaluated by a pathologist in retrospective fashion with that of the routine evaluation at the time of performing bone marrow biopsy. We then compared these results with those obtained by computer-aided histomorphometry in 28 patients in nPR. There was significant correlation (P < 0.05) between pathologists as well as between pathologists and histomorphometry. Upon correlation with clinical characteristics, there was significant correlation (P 0.01) between marrow involvement before therapy and white blood cell counts (wbc), hemoglobin (hgb), absolute lymphocyte counts, and beta2-microglobulin (beta2-m) but none of these parameters correlated with the lymphoid infiltrate at the end of three or six courses of therapy. more importantly, lymphoid infiltration after three and six courses did not correlate with time to progression (ttp) or overall survival (os). however, patients with >70% marrow involvement before therapy had a significantly shorter TTP (P = 0.02). All 91 patients showed similar results. However, we found reverse correlation between marrow lymphoid infiltrate at the end of three courses and OS (P = 0.01).

Aged↗