Endogenous megakaryocyte and erythroid colony formation from blood in essential thrombocythaemia.

The in vitro cultures of haematopoietic progenitors have been reported to be useful in the diagnosis of myeloproliferative disorders since the so-called endogenous erythroid and megakaryocyte colony formation has, in most studies, been found in these diseases. In order to know their value as diagnostic criteria in essential thrombocythaemia (ET) we have studied megakaryocyte (with and without phytohaemagglutinin-stimulated leucocyte conditioned medium) and erythroid (with and without erythropoietin) colony formation in vitro by progenitors from blood in 60 patients with ET and in ten with reactive thrombocytosis (RT) using the methyl-cellulose assay. Out of 60 ET patients endogenous megakaryocyte colony growth was observed in 38 (63%) and endogenous erythroid growth in 42 (70%). None of the patients with RT or any of the controls showed either type of endogenous growth. Fifty-five (91%) of the patients with ET showed megakaryocyte and/or erythroid endogenous colony formation whereas five (9%) did not have any kind of endogenous colonies, although cultures were performed sequentially. In conclusion, a positive endogenous megakaryocyte and/or erythroid colony growth from blood is a frequent and characteristic finding in ET patients and should be used as a useful marker in this disease.

Major vascular complications in essential thrombocythemia: a study of the predictive factors in a series of 148 patients.

To determine the clinicohematological factors predictive for the appearance of major vascular complications (MVC) in patients with essential thrombocythemia (ET), 148 consecutive such patients were retrospectively assessed for the development of MVC during a median follow-up of 58.5 months. Seventy-seven patients had vascular risk factors, and 37 a history of MVC at ET diagnosis. Forty-nine MVC were registered in 33 patients during the follow-up period. The actuarial probability of MVC was 27% at 6 years in the whole series, 35.6% for patients above 60 years, and 21.4% for patients younger than 60 years, whereas only one of the 36 patients younger than 45 years had MVC. At multivariate analysis, age >60 years, history of major ischemia and hypercholesterolemia were the variables associated with an increased MVC risk. These results suggest that all ET patients above 60 years should be treated, whereas in younger patients treatment decisions should be primarily based on the existence of risk factors for MVC.

Burkitt's type translocation in multiple myeloma.

We report a case of multiple myeloma with a t(8;22)(q24;q11) found during the progression of the disease. The relation between the association of a Burkitt's type translocation with cytological characteristic features is presented. To our knowledge, there is no report of a multiple myeloma with t(8;22)(q24;11).

A new chromosomal anomaly associated with mature B-cell chronic lymphoproliferative disorders: del(7)(q32).

Among 63 patients with chronic lymphoproliferative disorders (CLPD) studied cytogenetically in our laboratory, four showed a del(7)(q32); in two it was the sole cytogenetic anomaly and in two it was part of a complex karyotype. We suggest that despite the rarity of this anomaly, it could be related to CLPD.

Two new cases of near-tetraploidy in adult acute myeloid leukemia.

Tetraploid or near-tetraploid karyotype has been described rarely in hematologic neoplasms. Herein we report two new cases of adult acute myeloblastic leukemia, M0 and M1 FAB subtypes that showed near-tetraploid clones that were studied with conventional cytogenetics and in situ hybridization (ISH). We compare our new cases with those previously reported.

Cytogenetic abnormalities in 13 patients with multiple myeloma.

Cytogenetic analysis was successfully performed in 45 consecutive multiple myeloma (MM) patients. Cytogenetic abnormalities were observed in 13 of 45 patients (29%). Eleven patients showed numerical changes and 9 showed structural abnormalities in chromosomes 5, 9, 11, 14, 15, and 19 were most frequently gained. Structural abnormalities preferentially involved chromosomes 6, 13, and 14.

Cytogenetic studies in five patients with Sézary syndrome.

A cytogenetic study was performed in five patients with Sézary syndrome. Metaphases were obtained from a phytohemagglutinin-stimulated lymphocyte culture. The five patients showed abnormal karyotypes. The chromosomes preferentially involved in numerical aberrations were chromosomes 10 (monosomy) and 13 (monosomy); involved in structural changes were chromosomes 1, 2, 4, 6, and 14. In our series, all patients showed progression of the disease.

Cytogenetic studies in acute nonlymphocytic leukemia.

Cytogenetic studies were performed in 74 untreated patients with acute nonlymphocytic leukemia (ANLL) between 1985 and 1988. Among 56 patients who were examined successfully at the time of diagnosis, 36 had abnormal karyotypes (64.2%). The distribution of chromosome abnormalities was uneven, according to the categories of the French-American-British (FAB) nomenclature. The highest frequency of chromosome abnormalities was observed in ANLL M4 with bone marrow (BM) eosinophilia (M4Eo). Numerical changes were observed in 11 cases; chromosome 8 was most frequently gained (11 patients), whereas chromosome 7 was most frequently lost (4 patients). Structural rearrangements were detected in 18 patients. Involvement of 16q22 was noted in 7 patients, 5q- was noted in 5, t(8;21) in 3, t(1;7) in 2, del(20) in 2, and involvement of 11q23 was noted in 2. The inversion of chromosome 16 was restricted to the M4Eo subtype. This study identified a novel abnormality [inv(2) (p11.2q11.2)] that had not been reported previously by other investigators.

Cytogenetic studies in 112 cases of untreated myelodysplastic syndromes.

Cytogenetic studies were performed in 112 untreated cases of myelodysplastic syndrome (MDS) between 1985 and 1990. Among 112 patients who were examined at the time of diagnosis, 54 had an abnormal karyotype (48%). The highest frequency of chromosome abnormalities was observed in refractory anemia with excess of blasts (RAEB) and RAEB in transformation (RAEB-t) and the lowest in refractory anemia with ring sideroblasts (RARS) and chronic myelomonocytic leukemia (CMMoL). Numerical changes were observed in 19 cases and structural in 17; chromosome 8 was most frequently gained (11 cases), whereas chromosome 7 was most frequently lost (6 cases), 5q- in 14 (4 as a sole anomaly); involvement of 7q22 was seen in 3 cases, 11p in 2 patients, 11q in 3 (one patient as a sole anomaly), 12p in 4 (2 patients as a sole anomaly), i(17q) in 4 (3 patients as a sole anomaly), and complex chromosomal defects in 10 patients. If one takes into account the prognosis value, a complex karyotype and the presence of ring chromosomes were correlated with the worst prognosis, followed by -7/7q-; an intermediate prognosis corresponds to i(17q), 12p as a sole anomaly, +8 (as a sole anomaly or plus other anomalies), and involvement of 12p. Patients with a 5q- as a sole anomaly or with a normal karyotype, had the best prognosis.

Cytogenetic abnormalities in three patients with B-cell prolymphocytic leukemia.

We present the cytological features, conventional cytogenetics, and in situ hybridization (ISH) findings of three cases of B-cell prolymphocytic leukemia (B-PLL). The diagnosis was made according to the French-American-British (FAB) criteria. We considered a diagnosis of B-PLL when a predominance (> 50%) of lymphoid cells with coarse chromatin but prominent central nucleoli and more abundant cytoplasm than typical chronic lymphocytic leukemia (CLL) cells were present. B-PLL express strong SIg, B-cell antigens, and reactivity with the monoclonal antibody FMC7. Chromosome analysis was carried out on lymphoid cells from peripheral blood and, in one patient, from lymph node. The phytohemagglutinin (PHA) mitogen was used. ISH was performed with two types of probes: the biotin-labeled chromosome 12-specific alpha satellite DNA probe to detect trisomy 12, and biotin-labeled libraries of whole chromosomes 1, 7, and 14. Clonal chromosome abnormalities were found in all three patients; in one, a complex karyotype was observed. The most frequent recurrent abnormality was trisomy 12. Our results suggest that PLL usually presents with cytogenetic abnormalities. The finding of translocation (11;14) is noteworthy; chromosomes 1 and 3 are also involved.

Cytogenetic studies in seventy-six cases of B-chronic lymphoproliferative disorders.

The results of cytogenetic studies are reported in 76 patients with B-chronic lymphoproliferative disorders (B-CLPD): 60 patients with chronic lymphocytic leukemia (CLL), six with follicular lymphoma in leukemic phase (FLLP), five with splenic B-cell lymphoma with villous lymphocytes (SLVL), two with chronic prolymphocytic leukemia (CPL), two with hairy cell leukemia (HCL), and one with plasma cell leukemia (PCL). PHA (phytohemagglutinin), PWM (pokeweed mitogen), LPS (lipopolysaccharide from Escherichia Coli), TPA (phorbol 12-myristate acetate), IL6 (interleukin 6), and DxS (dextran sulfate) were used as mitogens. Mitoses were obtained in 75 cases. Clonal aberrations could be demonstrated in 34 cases (44%). In CLL, classical type, chromosomes 6, 11, and 13 were more frequently involved, whereas trisomy 12 was frequently found in CLL mixed-cell type, in FLLP, and CPL. In SLVL the deletion del(7)(q32) is noteworthy and miscellaneous chromosome abnormalities in the remaining patients were observed. Regarding the efficiency of mitogens, PHA turned to be the most effective in obtaining metaphases and in detecting clonal chromosomal aberrations.

Translocation (11;14)(q13;q32) and preferential involvement of chromosomes 1, 2, 9, 13, and 17 in mantle cell lymphoma.

We have studied 13 cases of histologically confirmed mantle cell lymphomas (MCL) combining cytological-immunological features with conventional cytogenetics and in situ hybridization (ISH) techniques. Peripheral blood smears and lymph node biopsies expressed the typical mantle zone pattern with alpha B-cell phenotype. Most of the cases (11 of 13) had lymphomatous cells in the peripheral blood. Chromosome analysis was carried out on lymphoid cells from peripheral blood and/or lymph node biopsies. Phytohemagglutinin (PHA) and phorbol 12-myristate 13 acetate (TPA) were used as mitogens. Biotin-labeled libraries of whole chromosomes implicated in complex karyotypes were used to improve their interpretation. Clonal chromosome abnormalities were found in 10 of 13 patients (77%); 7 of these had a complex abnormality. The most frequent recurrent structural abnormalities were: t(11;14)(q13;q32), involvement of chromosome 1 (der[1], del[1], dup[1]), chromosome 2 (del[2], der[2]), chromosome 9 (der[9], -9), chromosome 13 (add[13], t[13q]), and chromosome 17 (add[17], der[17], t[17q]). The most frequent numerical abnormalities were monosomy 21 and loss of the Y chromosome.

Expression of lymphocyte function-associated antigen (LFA)-1 in B-cell chronic lymphocytic leukemia.

We investigated the expression of the lymphocyte function associated (LFA)-1 adhesion molecule, recognized by the CD11a and CD18 monoclonal antibodies, in 53 patients with B-cell chronic lymphocytic leukemia (B-CLL) and in 37 controls. The mean percentage of control lymphocytes expressing CD11a and CD18 positivity was 92 +/- 5.5 and 90 +/- 8.7, respectively and, in patients with B-CLL, 14.2 +/- 10.3 and 14.8 +/- 10.3 respectively (p < 0.001). No statistical difference was found between CD11a and CD18 expression and the Rai clinical stages. In our experience a decrease of LFA-1 is a constant finding in B-CLL, in the early stages of the disease. It may, therefore, be useful to differentiate between slight increases of neoplastic cells and reactive blood lymphocytosis.

[Chronic T-cell lymphocytic leukemia. Report of two cases (author's transl)]. / Leucemia linfática crónica de células T. Presentación de dos casos.

Two patients with chronic lymphocytic leukemia of T-cell immunological origin are studied. One case was of the prolymphocytic variety, and the other corresponded to the "classical" type of chronic T-cell lymphocytic leukemia. From a morphological point of view what stood out was the hyperchromatic aspect of the cytoplasm of the lymphocytic proliferation. The high increase of acid hydrolases localized preferentially in the centrosomic area was the main cytochemical characteristic. Isoenzymatic study of leukocytic acid phosphatase showed a noticeable increase of band 3 and the absence of supernumerary band 3b. Immunological analysis revealed a significant decrease of the surface immunoglobulins and a rise in absolute terms in the number of lymphocytes forming spontaneous rosettes. In the case of the prolymphocytic variety what was particularly noticeable was the great number of lymphocytes bearing complement receptors. The combination of cytomorphologic, isoenzymatic and immunological data make it possible to differentiate between lymphoproliferative diseases of T and B-cell origin at the present time.

[Primary testicular lymphoma. A report of 3 cases]. / Linfoma primario testicular. Presentación de 3 casos.

The cases of three patients with primary testicular lymphoma, Ann Arbor IAE stage with the ages of 74, 72 and 60 years are presented. Histologic results demonstrated 2 cases of intermediate grade of malignancy and 1 of low grade. Immunohistochemical analysis for epithelial antigens was negative and the measurement of the serum levels of alpha-fetoprotein and beta-HCG was normal. LDH and beta-2-microglobulin were also normal. Chemotherapy was performed and the three patients remain alive and free of disease at 65, 32 and 19 months following diagnosis. The therapeutic results of the most important series were reviewed with the conclusion that treatment should be intensive, including orchiectomy plus chemotherapy even in apparently localized cases. The complementary role of radiotherapy is also discussed.

[Argyriasis. Report of a case (author's transl)]. / Argirosis. Descripción de un caso.

A case of argyriasis in a 45-year-old woman is reported. When the patient was 34 she took for a period of 25 months a silver-containing pharmacological product (colloidal silicon with 0.5 percent of silver) in order to treat an intestinal dyspepsia with diarrheic episodes. A few months after discontinuing the treatment a cutaneous pigmentation of a greyish-blue color extending over the whole body, developed. There was also discoloration of the nails, hair, and of the oral and gingival mucosae. The differential diagnosis with other conditions that also develop anomalies of cutaneous pigmentation was established. It is thought that the appearance of the silver poisoning is due to different factors such as the quantity of silver intake, the individual sensitivity to the metal, and the greater or lesser period of exposure to sunlight. The importance of the skin biopsy in order to confirm the diagnosis is commented on. Typical pathologic findings include the presence of silver granules in the basal membrane of sudoriparous glands, around the pilosebaceous follicles, and in the connective tissue. Lastly, the authors insist on the necessity to avoid the prescription of silver-salt containing drugs as far as possible, since the cutaneous pigmentation is irreversible.

[Complete clinical remission over 50 months of a patient with acute monocytic leukaemia (author's transl)]. / Remisión clínica completa de 50 meses de evolución en un paciente afecto de leucemia aguda monocítica.

A case of Schilling type pure acute monocytic leukaemia (M5 variety of the FAB classification) in a 38-year-old man is presented. The initial predominant clinical manifestation was an increase hypertrophic gingivitis. The cytological type was established according to the morphologic and cytochemical criteria currently in use. The patient was treated with daunomycin (60 mg/m2 one day) and ARA-C (100 mg/m2/12 hours for 7 days) in a 2-week interval cycles. Total remission was achieved after the fifth series. The series have been repeated over 4 years with intervals of up to 6 or 8 weeks. Complete haematologic remission has been constant, with normalization of the serum muramidase levels. A gingival biopsy taken at the same time has shown no evidence of leukaemic infiltration. The high incidence of malignancy in this cytological variety of acute leukaemia is pointed out; it is normally less sensitive to chemotherapy than the myeloid types. Remission has been total over a long period of time, which is exceptional in this type of leukaemia. The mean survival rate as recorded in the literature is only a little over 3 months.

[Immunoblastic sarcoma (author's transl)]. / Sarcoma inmunoblástico.

A case of immunoblastic sarcoma in a 56-year-old man is presented. He had no history of predisposing diseases. His clinical condition was typical of a highly aggressive disseminated malignant lymphoma and he presented important heterogenous hypergammaglobulinemia. The patient died 9 months after the onset of the disease, following brief and incomplete response to various chemotherapeutic associations. The importance of cytological and cytochemical studies of lymph node by touch prep is stressed, since this condition could have been misdiagnosed, in our case, with a malignant histiocytosis. The cell proliferation was shown cytochemically to be of B-lymphoid origin, not histiocytic. It was a monomorphic and nearly massive proliferation of large, intensely basophilic, nonphagocytolytic cells; reactions to naphthol-As-D-acetate esterase, acid phosphatase, beta-glucuronidase, and Perl's stain were negative. The relatively few phagocytolytic cells were shown cytochemically to be normal, true histiocytes, not identifiable with the atypical proliferating cells. This was an essential fact in establishing the diagnosis of immunoblastic sarcoma. In light of today's knowledge, the authors believe that immunoblastic sarcoma is a lymphomatous condition which should be distinguished from centroblastic lymphadenopathy. Lastly, they comment on a retropsective study of lymphomas previously catalogued as reticulo-sarcomas, which has shown that the majority of cases were centroblastic lymphomas and some were immunoblastic sarcomas.

[Malignant hypereosinophilic syndrome. Report of an exceptional case (author's transl)]. / Síndrome hipereosinofílico maligno: presentación de un caso excepcional.

The case of a 43-year-old man with a highly malignant hypereosinophilic syndrome is reported. The condition is classified as such according to Hardy and Anderson's criteria, accepted by many other authors. Other diseases of known etiology which may present high levels of eosinophils in the peripheral blood, such as parasitosis, allergies, neoplasias, collagenosis, etc., were discounted beforehand. The difficulties in distinguishing between these diseases are discussed; they are often accompanied by clinical manifestations which also arise in very different conditions including eosinophilic leukemia, Engfeldt and Zetterström's eosinophilic collagenosis, Löffler's fibroplastic endocarditis, etc. A particularly striking feature of this condition is the formation of large tumor masses of mature eosinophils. They begin in various bones, which they destroy almost completely, and invade the surrounding tissues, destroying them as well. These tumors act similarly to malignant eosinophilic myelocytomas, a fact which has not been reported previously in the literature as far as we know. Although the eosinophils act as though they were neoplastic, they maintain the characteristics of mature cells, both cytomorphologically and ultrastructurally as well as cytochemically (consistently chloroacetate esterase negative). The tendency to diagnose eosinophilic leukemia solely on the basis of the malignancy of the condition and a tissue infiltration of eosinophils without determining the existence of cytologic and/or cytochemical anomalies of the cells showing them to be leukemic is discussed. The authors were unable to find any reports in the literature in which the eosinophils were presented with unmistakeably blastic cellular characteristics. Various nosologic considerations are offered.

[Pseudohemopathy caused by rhabdomyosarcoma]. / Seudohemopatía por rabdomiosarcoma.

A 26-year-old male with a primary rhabdomyosarcoma of maxillary sinus is reported. The tumor was initially mistaken for an anaplastic Ki-1 positive anaplastic lymphoma in the histological preparation, owing to its high indifferentiation degree. After a smear study it was categorized as IEA, and chemotherapy of CHOP type was started; after two courses, local telecobalt therapy was given. After this was completed, the disease showed a progression, involving the bone marrow and resulting in clinical and cytological features consistent with acute leukemia. At that time we saw the patient for the first time. He is presently in complete remission after having started polychemotherapy of CVADIC type. After a commentary on the major study steps that led to the diagnosis, the crucial role of electron microscopy and, particularly, immunocytology for the correct identification of anaplastic tumors is emphasized.