p53 abnormalities in splenic lymphoma with villous lymphocytes.

The incidence and role of p53 abnormalities have not been reported in splenic lymphoma with villous lymphocytes (SLVL), the leukemic counterpart of splenic marginal zone lymphoma. Because p53 abnormalities correlate with progressive and refractory disease in cancer and isochromosome 17q has been described in SLVL, a low-grade lymphoma that behaves aggressively in a minority of patients, this study investigated p53 changes by molecular and immunophenotypic methods in samples from 59 patients. The p53 deletion was analyzed by fluorescence in situ hybridization, and p53 protein expression was assessed by immunocytochemistry in 35 of 59 cases and by flow cytometry in 20 of 35 patients. Ten patients (17%) had a monoallelic p53 loss, 3 (9%) of 35 nuclear protein expression by immunocytochemistry, and 2 (10%) of 20 by flow cytometry. Two patients had both deletion and protein expression. Direct sequencing of all p53 exons was used to delineate mutations in 9 of 11 patients with an identified abnormality. Mutations, both compromising p53 DNA binding, were identified in the 2 patients with deletion and protein accumulation. Kaplan-Meier analysis revealed a significantly worse survival for patients with p53 abnormalities. Although p53 abnormalities are infrequent in SLVL, they underlie a more aggressive disease course and poor prognosis. (Blood. 2001;97:3552-3558)

Immunophenotype changes and loss of CD52 expression in two patients with relapsed T-cell prolymphocytic leukaemia.

T-cell prolymphocytic leukaemia (T-PLL) is an aggressive disease often resistant to conventional chemotherapy. Long lasting remissions with the monoclonal antibody CAMPATH-1H (anti-CD52) have been documented. We describe two unusual T-PLL patients treated successfully first with CAMPATH-1H in whom, at the time of relapse, the cells underwent a phenotypic switch with loss of CD52 expression. In one of them, cytogenetic analysis demonstrated the same chromosome abnormalities in the cells at diagnosis and relapse. The reasons for the immunophenotypic changes are unknown but it is likely that loss of CD52 antigen expression contributed to the resistance to CAMPATH-1H in one of the patients when re-treated.

[Organizational models for the hematology areas of the district hospitals of Catalonia]. / Modelos de organización en las áreas de hematología de los hospitales comarcales de Catalunya.

PURPOSE: The haematological assistance in Catalonia is based upon the district hospitals, in the first step, and the stage III hospitals located usually in higher population nuclei, in the second step. The purpose of this work was to analyse the resources of the "primary haematological assistance" network provided by the district hospitals, to evaluate them and to propose a model for their organisation. MATERIAL AND METHODS: An enquiry was carried out to all members of the Grup de Treball d'Hospitals Comarcals de Catalunya (Catalonia's District Hospitals Task Force). The evaluable data included demographic figures of the population assisted, personnel of each haematological area, organising structure, clinical activity, cytomorphology, blood banks, laboratories and continuous formation activities. RESULTS: The enquiry was answered by 15 of the 21 district hospitals (71.4%) with haematologists in Catalonia. The population assisted in those hospitals is 2,100,000 (ranging between 55,000 an 450,000). All centres are integrated in the National Health network. Eleven of the hospitals analysed have only one haematologist (73.3%). If his dedication is 100% of the time, this would represent a doctor for 105,000 people. The time devoted to work is 690 hours a week for all the population, with a mean of 3,043. Four patients assisted per hour. The total number of hospital beds is 3,353 (50-450), with a mean number of 1 haematologist for every 167.6 beds. The number of patients hospitalized due to blood diseases ranges between 3 and 13 per month. Six of the 15 centres are adjunct to the outpatient clinic. Two centres have a blood bank and 7 have developed an autotransfusion programme. All the centres but one perform oral anticoagulant treatment follow-up, the number of patients assisted ranging from 20 to 210 per week. None of the hospitals has a separate Haematology Service; in most of them haematology is structurally and functionally dependent from Laboratories and in some there is a mixed Laboratory/Internal Medicine functional organisation, depending of the Medical Direction. No haematologist is ever on call specifically for his specialty. Continuous formation activities are carried out in 9 of the 15 centres (60%). COMMENT: Several measures are proposed to improve the haematological assistance, acting on different levels: continuous formation, patient flows and circuits, resident doctors training, anticoagulant treatment network, organisation models, credit cards from the Spanish Association of Haematology.

[Granulocytic sarcoma: a study of 5 cases]. / Sarcoma granulocítico: estudio de cinco casos.

Granulocytic sarcoma (GS) is a solid tumor of extramedullary localization constituted by immature precursors from the granulocytic series. GS may be diagnosed in different malignant blood diseases involving the granulocytic series, acute non lymphoblastic leukemia (ANLL) being the most frequent, followed by myelodysplastic syndromes (MDS) and chronic myeloproliferative syndromes, specially chronic myeloid leukemia (CML) in blastic crisis. Although the diagnosis of GS is suspected with conventional cytologic and anatomopathologic studies, histochemical staining and immunohistochemical techniques are often required for definitive diagnosis. Five cases (4 males, 1 female; age range 22-77 years) diagnosed with GS in one center over a period of nine years (1984-1993) are described. The GS were located in the lymph nodes, the jaw, paravertebral region, gallbladder and retroperitoneum, respectively. Two patients had refractory anemia with excess of blasts (RAEB). Three patients had ANLL; in one GS constituted the form of relapse, in another GS presented at the time of diagnosis and in the remaining patient GS preceded the diagnosis of ANLL. All the patients died from 2 to 8 months after diagnosis of GS with no response to treatment being observed. Immunohistochemical study of the tumor was performed in 4 patients, being positive for lysozyme and the monocytic MAC-387 monoclonal antibody. Immunocytochemical study of the tumor blasts was carried out with positivity for CD15 being observed. Although uncommon, GS should be suspected in patients with ANLL or MDS with tumors of any localization and at any time during its evolution. Immunocytochemical and immunohistochemical studies are of great value to differentiate GS from other tumors, particularly anaplastic non Hodgkin's lymphomas.

[Pseudotumorous hyperplasia of the caudate lobe of the liver in a patient with Alagille syndrome]. / Hiperplasia seudotumoral del lóbulo caudado del hígado en una paciente con síndrome de Alagille.

The Alagille's syndrome consists in hypoplasia of the intrahepatic biliary ducts associated to congenital abnormalities of different organs. It is usually diagnosed in infancy due to cholestasis with good prognosis. The case of a 31-year old women who presented prominent chin, micrognathia, flattening of the nasal bone, infundibular stenosis of the pulmonary artery and cholestasis is reported. Ultrasonography demonstrated a lesion in the space of the hepatic caudate lobe with punction showing sinusoidal dilatation and infiltration of some portal spaces by lymphocytes, eosinophils and neutrophils. Samples of liver tissue obtained during laparotomy showed an absence of intrahepatic biliary ducts in the right and left lobes and preservation of those of the caudate lobe, which was also increased in size with a pseudotumoral appearance. The patients was asymptomatic with slight anicteric cholestasis at 16 months of diagnosis. The rarity of these forms of Alagille's syndrome with areas free of hypoplasia of the intrahepatic biliary ducts are of note.