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[Oculomotor nerve and trigeminal nerve involvement demonstrated by Gd-DTPA-enhanced MRI in acute lymphoblastic leukemia: a case report].

Magnetic Resonance Imaging (MRI) is considered a useful procedure for evaluating the intracranial diseases. Leukemic infiltration in either the oculomotor or trigeminal nerve is rarely seen by MRI. We herein describe the diagnostic assessment and outcome of an adult patient suffering from acute lymphoblastic leukemia (L2, FAB). An 18-year-old female was suspected to have ALL. She complained of nausea, vomiting, and double vision for a month, and further examination was required. Fiber gastroscope examination revealed no abnormal lesions in the upper gastrointestinal tract. Furthermore, a plain brain CT indicated no abnormalities in the brain. However, examination of a Gd-DTPA enhanced MRI and the liquor revealed that she had leptomeningeal leukemia with oculomotor and trigeminal nerve infiltration. Systemic administration of methotrexate (MTX) and cytarabine, and intrathecal injection of MTX were partially effective. Repeated Gd-DTPA enhanced MRI showed the shrinkage and reduced enhancement of oculomotor and trigeminal nerve, parallel to the improvement in the liquor. This case demonstrates the importance of MRI not only in the evaluation of therapy, but also in the early diagnosis of central nervous system leukemia.

Adolescent↗

[The cytological and biochemical aspects of studying the cerebrospinal fluid in patients with chronic myeloleukemia].

The investigation of cell composition and different biochemical parameters (ceruloplasmin, lactate dehydrogenase, aldolase, ferritin, beta-2-microglobulin) in cerebrospinal fluid has been performed in 37 patients with chronic myeloid leukemia at different clinicohematological stages. The age of the patients ranged from 16 to 67 years. CNS involvement has been diagnosed in 8 (21.6%) patients by clinical and cytological criteria and in 5 (13.5%) patients on the basis of changes in liquor cytograms and in biochemistry. Morphological substrate of leukemic infiltration may be represented by blast cells and cells of granulocytic line of all stages of differentiation. Direct correlation has been established between ferritin and beta-2-microglobulin levels in liquor and its cytological patterns. This permits a conclusion on possible usage of liquor concentration of beta-2-microglobulin and ferritin measurements as additional tests in the diagnosis of neuroleukemia in chronic myeloid leukemia.

Adolescent↗

Involvement of the lacrimal drainage system by leukemia or lymphoma.

PURPOSE: To determine the clinical characteristics and outcomes of patients with leukemic or lymphomatous involvement of the lacrimal drainage system (LDS). METHODS: A computerized retrieval system was used to identify patients with histologically proven leukemic or lymphomatous involvement of the LDS. Medical records were reviewed. RESULTS: Biopsies of the lacrimal sac or nasolacrimal duct obtained during dacryocystorhinostomies (DCR) performed at the Mayo Clinic (Rochester, Minnesota) between January 19, 1989, and August 26, 1997, were positive for leukemia or lymphoma in 11 patients (15 LDS). Ten patients had previously diagnosed leukemia or lymphoma; the interval between the diagnosis of systemic disease and DCR averaged 5.8 years (range, 7 months to 13 years; median, 5 years). The median age at the time of LDS involvement was 72 years (range, 49 to 85 years). Seven patients (64%) were women, and all were white. The median postoperative follow-up after DCR was 38 months (range, 10 to 65 months). Eight patients had leukemic infiltration of the LDS, 2 patients had B-cell lymphoma, and 1 patient had cutaneous T-cell lymphoma. Four patients had bilateral LDS involvement, and the remainder had unilateral disease (right eye, 1 patient; left eye, 6 patients). The most common initial presentation, in 9 patients (82%), was epiphora. Lacrimal irrigation of 2 LDS was deferred because of acute dacryocystitis. Of the remaining 13 systems, 8 were completely obstructed. The blockage was low (in the lower sac or in the nasolacrimal duct) in 6 systems and high (in the upper sac or common internal punctum) in 2 systems. Four LDS were anatomically patent to irrigation but were functionally obstructed. Chemotherapy was the primary treatment in 7 patients, whereas 4 patients underwent radiation therapy. Nine patients responded well to treatment, with alleviation of signs and symptoms, and none of these patients had local recurrence during the follow-up interval. CONCLUSIONS: Leukemic or lymphomatous involvement of the LDS is an unusual cause of tearing in elderly patients, but it should be suspected in patients with known systemic disease. Treatment comprising multiple interventions improves the signs and symptoms of this complication of lymphoproliferative disorders in most patients.

Aged↗

Leukemia cutis in acute promyelocytic leukemia: report of three cases after treatment with all-trans retinoic acid.

Acute promyelocytic leukemia (APL) is a distinct form of acute myelogenous leukemia characterized by an abundant number of abnormal progranulocytes, a severe coagulopathy and a distinct chromosomal abnormality t(15;17). Recently all-trans retinoic acid (ATRA) has been shown to induce complete remissions in APL. We report three patients with APL treated with ATRA, who at the time of relapse had leukemic infiltration of the skin (leukemia cutis), a manifestation which we had not seen previously in over 60 patients with APL treated with chemotherapy alone and has only rarely been reported in the literature. We hypothesize that ATRA treatment for APL may be associated with an increased incidence of extramedullary disease at the time of relapse, which may be mediated through an increase in expression of adhesion molecules. Careful observation for extramedullary relapses in patients treated with ATRA for APL will be needed to confirm our observation.

Adult↗

Transient leukemia with trisomy 21: description of a case and review of the literature.

Transient myeloproliferative disease (TMD) is often associated with a trisomy 21 cell line, but it is not always associated with clinical signs of Down syndrome. We report on a phenotypically normal newborn boy who presented with a high white blood cell count, undifferentiated blasts, and cutaneous leukemic infiltrates and compare this patient with the literature on TMD and trisomy 21. Chromosome analysis of bone marrow, and subsequently of skin fibroblasts, documented constitutional mosaicism for trisomy 21. A decrease in the frequency of blast cells paralleled a decrease in cells demonstrating trisomy 21 in hematopoietic tissues, and a complete clinical recovery was seen without the use of chemotherapy. Recognition of this transient form of congenital leukemia is important to prevent the unnecessary use of toxic chemotherapeutic agents in such patients.

Bone Marrow↗

Low back pain and myalgias in acute and relapsed mast cell leukemia: a case report.

Mast cell leukemia is a rare, severe disease that may manifest through an array of clinical presentations, including vasomotor flushing and hypotension. Leukemic infiltrate of muscle and bone may rarely occur, resulting in nonspecific myalgias, bony pain, and neuropathic pain secondary to compression of nerves by bone. Mast cell leukemia as a clinical entity has not been well described. We present the case of a 25-year-old man with a remote medical history of germ cell tumor who was initially diagnosed with mast cell leukemia after presenting with low back pain. One and a half years later, the patient presented with a chief complaint of back pain and myalgias and was found to have relapsed mast cell leukemia. Medical management and, specifically, rehabilitation of these patients can be extremely difficult. This report shows the complex management of patients with mast cell leukemia.

Adult↗

[Megakaryoblastic leukemia which developed from therapy-related MDS with myelofibrosis].

A 56-year-old man had a leiomyosarcoma of the small intestine in 1987. After surgery, he received cyclophosphamide for 2 years. In December, 1990, he exhibited severe pancytopenia. His hematological data were as follows: Hb 7.4g/dl, ret. 0.8%, WBC 1,700/microliters with leukoerythroblastosis and 2.8 x 10(4)/microliters platelets. A bone marrow aspiration was a dry tap. A bone marrow biopsy specimen showed a hypercellular marrow with myelofibrosis, leukemic infiltration (10.2%) and slight dyserythropoiesis. Both PPO and GPIIb/IIIa reaction were positive for blast cells and atypical megakaryoblasts. A diagnosis of MDS with an abnormality in megakaryocytic lineage was made. The patient was treated with 1,25-dihydroxy-vitamin D3, however this therapy was temporary and he developed into acute megakaryoblastic leukemia (M7). This report suggested that some cases of therapy-related leukemia (TRL) mainly involve megakaryocytic lineage and are diagnosed as MDS with myelofibrosis which transform to M7. The fact that PAS stain of erythroblasts in the patient reported here was positive may suggest involvement of development of more precise immunological markers of differentiation and EM study will permit better diagnosis of TRL and may therefore facilitate new therapeutic approaches.

Chemotherapy, Adjuvant↗

Chronic lymphocytic leukemia presenting with symptomatic central nervous system involvement.

Leukemic infiltration of the central nervous system (CNS) resulting in neurological manifestations is a rare complication of chronic lymphocytic leukemia (CLL). Furthermore, symptomatic CNS involvement as the initial presentation of previously undiagnosed CLL is extremely rare. In the present report, the authors describe a case of an 89-year-old female previously diagnosed with Alzheimer's disease who suddenly developed rapidly worsening mental changes. Cytological and immunocytological examinations of the lymphoid cells present on the cerebrospinal fluid (CSF) revealed CNS involvement by a clonal B-cell lymphoproliferative disorder, most consistent with de novo B-CLL expressing kappa light chain restriction. Subsequently, flow cytometric analysis done on the peripheral blood lymphocytes confirmed the diagnosis of B-CLL in this patient. Thus, this study shows the potential usefulness of immunocytological evaluation in detecting monoclonal lymphoid populations on CSF samples in adult patients presenting with altered mental status and CSF pleocytosis of lymphocytes.

Aged↗

Analysis of 135 autopsy eyes for ocular involvement in leukemia.

To explain the marked variation in the reported incidence of how often leukemic cells infiltrate the eye in fatal cases of leukemia, we tested the hypothesis that ocular leukemic infiltration is related to the peripheral leukocyte count during the final hours of life. We reviewed tissue sections, as well as autopsy and clinical records, from 135 patients who had fatal leukemia and had their eyes examined after death at Duke University Medical Center. Infiltrates of leukemic cells were found in the eyes of 42 of 135 patients (31.1%), with the choroid being the most frequently involved site. We detected a significant positive correlation between the ocular leukemic infiltration and an agonal leukocyte count as well as the severity of systemic disease. Differences in the agonal circulating leukocyte count may partly explain variations in the incidence of leukemic infiltrates in different postmortem studies.

Choroid↗

[Salivary gland lymphomas].

This tutorial focuses on malignant lymphomas and inflammatory conditions as potential precursors of primary malignant lymphomas in salivary glands. Salivary glands display a mucosa-associated lymphoid tissue and are often associated with intra- and periglandular lymph nodes. Inflammation of the glands may variably produce duct ectasia, lymphoepithelial lesions, atrophy, and fibrosis. Primary lymphomas of the salivary glands may develop on the basis of autoimmune sialadenitis and comprise most frequently marginal zone lymphomas, less often monocytoid lymphomas or other lymphoma entities. In a large proportion of cases, lymphoma infiltrates are attributable to extraglandular lymphomas either as a leukemic infiltrate with diffuse enlargement or as a localized manifestation of primary nodal non-Hodgkin lymphomas. Diagnosis is based on conventional histology and immunohistology.

Humans↗

Bilateral optic disk edema and blindness as initial presentation of acute lymphocytic leukemia.

PURPOSE: To report bilateral optic disk edema and blindness as the unusual initial presentation of acute lymphocytic leukemia (ALL) in an adult. METHODS: A 19-year-old man presented with a history of headaches, back pain, and 10 days of worsening vision that progressed to blindness. Ocular examination revealed light perception acuity in the right eye and no light perception in the left eye. Fundus examination revealed bilateral profound optic disk edema, tortuous vessels, and retinal hemorrhages. Acute lymphocytic leukemia was diagnosed with complete blood count and bone marrow biopsy. Head computed tomography and magnetic resonance imaging, were normal. Lumbar puncture revealed normal opening pressure. Ocular ultrasonography showed bilateral optic nerve enlargement. DESIGN: Interventional case report and literature review. RESULTS: The presumptive diagnosis of leukemic infiltration of the optic nerves was made, and urgent radiotherapy, intrathecal methotrexate, and intravenous daunorubicin were instituted. Visual acuity improved to hand motions in the right eye. CONCLUSIONS: Acute lymphocytic leukemia can rarely present in adults as visual changes due to leukemic optic nerve infiltration. Radiation treatment should be considered as an urgent treatment modality for this rare condition.

Adult↗

[Magnetic resonance imaging: more sensitive method in the detection of leukemic central nervous system infiltration].

PURPOSE: To define the ability of magnetic resonance imaging (MRI) in identifying leukemic infiltration of central nervous system (CNS) in children. METHODS: The MRI of CNS was carried out in 54 leukemic children (mean age 8.9 years). The results were compared with CSF cytology and neurological examinations. RESULTS: Leukemic involvement of CNS (1 intracerebral infiltration, 5 meningeal intracranial infiltration, and 5 cases of intraspinal infiltration) was found in 11 children (20.4%)--6 of them were before treatment. Blasts in CSF were found only in 3 examined children. CONCLUSIONS: The results of the study implicate the importance of routine MRI screening in leukemic children. We found especially important to perform the first examination before the onset of treatment because therapy may cause very quick regression of leukemic infiltration in CNS.

Adolescent↗

Leukemic iritis with hypopyon.

A patient with acute lymphoblastic leukemia who had received CNS sanctuary treatment with cranial X-irradiation and intrathecal methotrexate displayed his first sign of relapse as iritis with malignant hypopyon. Treatment included topical and subconjunctival corticosteroids and local X-irradiation. Leukemic infiltration of the iris may be the first sign of leukemic relapse. Slit-lamp examination should be performed in all leukemic patients with ocular symptoms.

Adult↗

[Leukemia of a still-born child (author's transl)].

A case of a stemcell-leukemia of a mature male macerated still-born child is described. The mother, a 20-year-old healthy bipara, a milker-maid by profession, had a normal hemogram. There was no evidence of blood group incompatibility. The autopsy of the fetus showed an excessive tumorous enlargement of the pancreas caused by the leukemic infiltration (Fig. 1). The microscopic examination of the placenta showed leukemic cells in the fetal blood vessels and the villous stroma (Fig. 2). In 1966 Werner compiled from literature 28 cases of true connatal leukemia and added a case of his own. From the newer accessible literature we collected further 19 reports (Table). In 7 of the 49 cases the connatal leukemia appeared together with Down's syndrom.

Acute Disease↗

Evaluation of CI-973, a platinum analogue, in refractory or relapsed acute leukemia.

The purpose of the study was to define the maximally tolerated dose (MTD), major toxicities, and possible antitumor activity of CI-973 a new platinum analogue, in patients with refractory or relapsed acute leukemia. CI-973 was given as a 5-day continuous infusion every 3 to 4 weeks to patients with refractory or relapsed acute leukemia, at doses ranging from 150 mg/m2 to 1350 mg/m2 per course. Thirty-six patients were treated including 18 patients with acute myelogenous leukemia (AML), four with acute lymphocytic leukemia (ALL) and 14 with chronic myelogenous leukemia in blastic phase (CML-BP). Severe gastrointestinal and renal side-effects were the dose-limiting toxicities occurring in four of five patients treated with CI-973 1200 to 1350 mg/m2 per course. At the MTD of 1000 mg/m2 per course, three of 13 patients treated (23%) had moderate to severe nausea and vomiting, three (23%) had moderate diarrhea and one had moderate mucositis. Among 21 patients treated at > or = 1000 mg/m2 (15 AML, 6 CML-BP) no objective complete or partial responses were observed. Twelve of 18 patients (66%) with evaluable marrows on day 14 showed significant suppression of marrow blasts percentage and marrow leukemic infiltrate percentage. Tests for measurement of DNA adduct formation in leukemic cells in vivo after CI-973 therapy, and in vitro following exposure of leukemic cells to CI-973 were developed. This study defined the MTD of CI-973 to be 1000 mg/m2 by continuous infusion over 5 days every 3 to 4 weeks in patients with refractory or relapsed acute leukemia. Gastrointestinal and renal side-effects were dose-limiting. No objective responses were noted in this heavily resistant population. Correlations between CI-973-induced DNA adduct formation and individual patient response to CI-973 will help to define its role in leukemia subsets.

Acute Disease↗

Acute myelogenous leukemia presenting as atypical mastoiditis with facial paralysis.

Symptomatic otologic involvement by leukemic infiltration is unusual, most often occurring in the already-diagnosed leukemic patient as postauricular mass, acute hemorrhagic otitis media, mastoiditis, cranial neuropathy, vertigo, hearing loss, or leptomeningitis. We think ours is the first reported patient whose leukemia presented as atypical mastoiditis and facial paralysis due to granulocytic sarcoma (chloroma). At mastoidectomy, tan lobulated rubbery tumor filled the mastoid antrum and middle ear cleft. Complete remission and full return of facial nerve function was achieved with 2500 R local radiation and systemic chemotherapy. We discuss the role and extent of surgery in atypical acute mastoiditis when unsuspected middle ear and mastoid tumor, with inconclusive intra-operative histopathologic data, is found.

Adolescent↗

Effects of 5-fluorouracil treatment of rat leukemia with concomitant inactivation of cobalamin.

The cytostatic activity of 5-fluorouracil (5-FU) can be modified by the addition of reduced folates, as well as antifolates. This is indicative of the complex involvement of folate metabolism in the effects of 5-FU. In the BN rat leukemia model, 5-FU treatment was combined with the inactivation of cobalamin (vitamin B12) by nitrous oxide (N2O). Exposure to nitrous oxide causes severe disturbance of folate metabolism through the inhibition of the cobalamin-dependent enzyme methionine synthetase, and leads to loss of folates from the cell. With regard to the effects on growth of leukemia, the addition of nitrous oxide did not antagonize 5-FU. On the contrary, therapeutic effects were enhanced by combined treatment, as was evident from a further reduction of leukemic infiltration in spleen and liver, from a decrease or even disappearance of leukemic cells in the peripheral blood, and from extended survival of rats. These findings were in accordance with metabolic studies in isolated leukemic cells of treated rats, in which combined treatment caused further impairment of thymidylate and DNA synthesis. Pretreatment with nitrous oxide, for a period of 3 days, was more effective than treatment after the administration of 5-FU. Folate levels, in plasma and intracellular, were reduced after combined treatment. It is concluded that in this leukemia, unlike observations in some models of solid tumors, the activity of 5-FU is enhanced with a depletion of folates. This effect is probably comparable to the combination of methotrexate pretreatment with 5-FU, and might be important to applications of 5-FU in combination chemotherapy of hematological neoplasms.

Animals↗

[Morphogenesis of experimental neuroleukemia].

22 mice with L-1210 leukemia treated with quinoline dibromide were studied histologically. Two ways of the development of leptomeningeal infiltrates in the brain are established. The first is due to the growth of uninhibited by treatment bone-marrow leukemic infiltrates (LI) of the skull, while the second-when the above infiltrates are suppressed-due to the proliferation of leukemic cells penetrating from the dura mater to the leptomeninges protected by the hematoencephalic barrier from the effect of anticancer drugs. when the recurrence of leukemia occurs the growth of bone-marrow LI continues resulting in the additional migration of leukemic cells to the leptomeninges. These ways of the leptomeninx LI formation should be taken into consideration in the leukemia treatment.

Animals↗