[Endomyocardial disease as the first manifestation of hypereosinophilic syndrome]. / Choroba endomiokardialna jako pierwsza manifestacja zespolu hipereozynofilowego.

A case of hypereosinophilic syndrome (HES) initially manifesting as endomyocardial disease in a 21-year-old man is presented. The diagnosis of HES was made according to the Chusid's criteria. Myeloproliferative disorders were excluded and corticosteroid therapy with prednisone at a dose of 1 mg/kg/d was started immediately. After 30 days of continuous corticotherapy the patient recovered completely. His blood eosinophil count decreased from 8740 cells/microL (48.7%) to 30 cells/microL (0.3%). Then, prednisone was discontinued gradually. During 18-month follow-up the patient was free from cardiovascular symptoms and his complete blood count was normal. We also present the current state of knowledge on the cardiovascular complications of hypereosinophilic syndrome.

ALK-positive diffuse large B-cell lymphoma: two more cases and a brief literature review.

Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare, recently defined tumor distinct in many aspects from ALK-positive anaplastic large cell lymphoma (ALCL). We present two additional cases of ALK+DLBCL recently diagnosed in our department and a review of literature. A 48-year old man presented with a large upper neck mass growing slowly over 18 months. Histologically the tumor was diagnosed as an ALK-positive diffuse large B-cell lymphoma. with plasmablastic features. Large, frequently intrasinusoidal tumor cells expressed CD138, EMA, weakly IgA and kappa, but were negative for other B-cell markers, T-cell markers and CD30. The ALK staining was cytoplasmic with the increased intensity in the Golgi area. At the diagnosis the patient manifested with the stage IIIB. Three courses of CHOP resulted in partial and only transient remission. The patient died of massive bleeding from his decomposing tumor 3 months after the diagnosis. A 49-year old man complaining of abdominal pain revealed abdominal lymphadenomegaly and a gastric infiltrate, involving the deep portions of the gastric wall. The tumor showed immunoblastic/anaplastic morphology, with some Reed-Sternberg-like cells positive for ALK. ALK immunostaining was cytoplasmic, weak in a routine immunostain, enhanced with double (proteinase + pressure cooker) antigen retrieval. FISH was consistent with the t(2;5)/nucleophosmin(NPM)-ALK rearrangement. The tumor demonstrated similar "null" B/T phenotype with positivity for IgA, lambda, EMA and LCA. The patient (stage IVB) currently undergoes chemotherapy. ALK-positive DLBCL affects mostly middle-aged men, shows generally poor but stage-dependent prognosis (at least 60% mortality rate), presents typically as a lymph node-based disseminated disease, and very rarely involves the bone marrow. Genetic studies showed that the majority of ALK+DLBCL cases are characterized by the clathrin (CLTC)-ALK fusion and in a few cases the NPM-ALK rearrangement has been found.

MRI-based evidence for myocardial involvement in women with hypereosinophilic syndrome.

PURPOSE: The aim of the study was to assess the presence and spectrum of cardiac abnormalities identified by cardiac magnetic resonance (CMR) in women with hypereosinophilic syndrome (HES) of undefined etiology, who present with normal electrocardiography (ECG) and transthoracic echocardiography (TTE) and no history of heart disease. METHODS: Ten women (mean age, 48 ± 14 years) with HES of undefined etiology, normal ECG and TTE, and no history of heart disease underwent CMR. RESULTS: CMR showed cardiac abnormalities in 6 subjects. Five patients had nonischemic late gadolinium enhancement (LGE) lesions within the left ventricular (LV) myocardium, and 3 patients demonstrated CMR evidence of myocardial inflammation. The LV ejection fraction was 68.5 ± 5.7%, and the end-diastolic volume index was 62.7 ± 14.7 mL/m(2). The maximum measured blood eosinophil count correlated with LVLGE volume (r = 0.80, P = 0.006) and was 11374 ± 6242 cells/µL and 4114 ± 2972 cells/µL (P = 0.047) in patients with and without LGE lesions, respectively. The actual blood eosinophil count in subjects with and without CMR evidence of myocarditis was 1058 ± 520 cells/µL and 354 ± 377 cells/µL (P = 0.04), respectively. CONCLUSIONS: Despite normal ECG, TTE, and absence of history of heart disease, women with HES of unknown etiology frequently demonstrate cardiac abnormalities on CMR, the presence and extent of which are related to blood eosinophil count.

Association between P-glycoprotein and lymphoid antigen expression on myeloblasts versus therapy response and survival in de novo acute myeloid leukemia: long-term follow-up results.

P-glycoprotein (PGP) over-expression on malignant cells is associated with poor prognosis and treatment outcome due to the development of a multidrug resistance phenotype. In this study, we analyzed the correlation between expression of PGP and lymphoid antigens (Ly) on leukemic myeloblasts versus response to therapy and survival in acute myeloid leukemia (AML). Fifty-one consecutive patients, aged 16-75 (median age 44.6 years), diagnosed with de novo AML between 1997 and 2000, and who received at least one induction chemotherapy course, were enrolled in the study. Expression of PGP on ≥ 10% of the myeloblasts (PGP(+)AML) at the time of diagnosis was observed in 21 patients (41%). The complete remission rate did not differ between PGP(+) (13/21) and PGP(-) (20/30) patients (62 vs. 67%). Twelve of the 51 patients (24%) were still alive after a median follow-up time of 11.5 years (range 10.7-13.1). The Ly(+)AML patients showed significantly better overall survival compared with Ly(-)AML patients (8/18 vs. 4/33 patients alive at the last follow-up, P = 0.003). The subgroup of patients with co-expression of PGP and Ly also showed better overall survival compared with PGP(+)AML patients without Ly expression (4/8 vs. 0/13 patients alive at the last follow-up; P = 0.04). Our results suggest that expression of lymphoid antigens on PGP(+) myeloblasts in AML can positively affect survival in AML patients, mainly due to a decreased relapse risk and better survival. Although the small number of patient may be perceived as a limitation of the study, the long follow-up period strengthens its value. Further prospective trials are needed to obtain more information concerning the association between PGP and lymphoid antigens in AML, which would put our results in their ultimate proper context.

A twelve-year follow-up study on a case of early-onset parkinsonism preceding clinical manifestation of Gaucher disease.

Mutations in the glucocerebrosidase gene (GBA1) cause Gaucher disease (GD) and are the most common genetic risk factor for the development of Parkinson's disease (PD). Here, we present a 12-year follow-up study of a male with GD and PD (diagnosed 24years ago), which PD preceded the clinical manifestation of GD by 12years. The patient is a compound heterozygote for mutations c.115+1G>A and c.1226A>G (IVS2 + 1/N370S) in the GBA1 gene. Imiglucerase had a beneficial effect on GD, but not on PD. Treatment with L-dopa and other PD drugs showed temporary efficacy but 2years later significant wearing-off phenomenon and dyskinesias appeared. Unilateral pallidotomy was performed with transient benefit. Cognitive decline appeared later and developed in to akinetic mutism. A lumbar puncture was performed to characterize the biochemical profile of cerebrospinal fluid (CSF). Analyses of monoamine metabolites levels in the CSF, determined by reverse-phase high-performance liquid chromatography, revealed remarkably low levels of all studied monoamine metabolites (HVA, DOPAC, 5-HIAA, MHPG). These data indicate that PD associated with GBA1 mutations may not only affect dopaminergic neurons, but also noradrenergic and serotonergic neurons. Of note, normal levels of P-tau, total tau and ß-amyloid (1-42) were detected on ELISA assay. Thus, the cognitive decline, akinetic mutism and moderate cortical atrophy found on the CT scan were not paralleled by any changes of dementia markers in CSF. This single case study extends the follow-up period and adds novel CSF information; however additional data on other patients with both PD and GD may help put our observations in its ultimate proper context.

Enzyme replacement therapy reduces Gaucher cell burden but may accelerate osteopenia in patients with type I disease - a histological study.

Enzyme replacement treatment (ERT) is effective in controlling the clinical and biochemical manifestation of type I Gaucher disease. Little is known on the evolution of bone marrow histology caused by ERT. We compared the pretreatment trephine bone marrow biopsies in five patients (F32, F41, F50, M55, and M46) with the control biopsies performed after 26-32 months of imiglucerase treatment. The planimetric estimates revealed significant decrease in Gaucher cell burden in all the patients. The post-ERT values ranged from 24% to 65% of the initial total volumes occupied by the Gaucher cells. This resulted mainly from disappearance of Gaucher cells, and to a lesser extent from their shrinkage. Normal hemopoiesis was markedly increased in four of five patients, fat tissue in all the five patients. Surprisingly, the estimated volumes of trabecular bone in the control biopsies were significantly smaller than in the pre-ERT trephines (0.61%, 0.64%, 0.64%, 0.97%, and 0.22% of the initial volumes, P = 0.043). The bone loss correlated rather with the degree of reconstitution of normal hemopoiesis than with the decrease in the Gaucher cell burden. The histological response did not correlate strictly with initial clinical parameters and the genotype, with different reactions to ERT in two sibs (cases 3 and 4). Particularly, ERT alleviated bone manifestations in all four patients with previous bone pains or fractures. ERT may accelerate progress of osteopenia in men and premenopausal women. The clinical significance of this phenomenon remains to be established. Its mechanism may be linked to increased osteolytic activity exerted directly or indirectly by regenerating hemopoietic cells.

Morphometric classification of hairy cell leukemia in bone marrow trephine biopsy.

OBJECTIVE: To analyze cytologic and histologic parameters in bone marrow trephine biopsy in an attempt to define heterogeneity of hairy cell leukemia cells. STUDY DESIGN: The study group consisted of 28 trephine biopsies. Immunohistochemistry for CD20 antigen was used. Image processing and measurements were performed with AnalySIS 3.0 image analysis system (Soft Imaging System GmbH, Germany) and custom built programs. For planimetric measurements of nuclei, automatic segmentation was implemented. The measured parameters were: surface area, perimeter, minimum, mean and maximum diameter, and a set of form factors. Relative volumes of bone trabeculae, adipose tissue, hematopoietic tissue and neoplastic infiltrate were assessed by the point counting method. Nuclear volume was measured by the point sampled intercept method. Bone marrow fibrosis was assessed using a curvilinear line test system. RESULTS: Significant variability of cell nuclei was found, and their classification into 3 types was possible. The relative frequency of those types was different in various cases and allowed subdivision of cases into 3 groups that differed in some clinical and histologic manifestations. CONCLUSION: The present study demonstrated the heterogeneity of cell populations of hairy cell leukemia.