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PubMed1980

Phagocytosis in acute leukemia.

The phagocytic potential of leukemic cells in various types of acute leukemia was studied. Cases included lymphoblastic leukemia, myeloblastic leukemia, myelomonocytic leukemia, monocytic leukemia, progranulocytic leukemia, blast transformation of chronic myelocytic leukemia, and unclassified leukemias. Cytochemical stains were used as an aid in classification. These included Sudan black B, naphthol AS-D chloroacetate esterase, alpha-naphthyl butyrate esterase, acid phosphatase, and periodic acid-Schiff. Phagocytosis was evaluated after incubation of leukemic cells with Candida albicans. Rare phogocytic activity was seen in lymphoblastic leukemia, unclassified leukemias, blast crises in chronic myelocytic leukemia, and progranulocytic leukemia. Myeloblastic leukemias were feebly phagocytic. Myelomonocytic leukemia and monocytic leukemia both exhibited marked phagocytosis which distinguished them from the other acute leukemias. Myelomonocytic leukemia could be differentiated from acute monocytic leukemia by its greater phagocytic capacity.

Candida albicans↗
PubMed1981

A cytochemical and immunohistochemical approach to malignant histiocytosis.

Malignant histiocytosis (MH) is a true histiocytic disorder, whose identification is still based on too broad morphologic criteria. Using routine histology, cytochemical and immunohistochemical techniques on involved lymph nodes, 15 cases of MH have been investigated. Pleomorphism and cellular atypia, phagocytosis, lack of cohesiveness between proliferating cells, sinusoidal involvement, and plasmacytic infiltrate were the most common histologic features. MGG-stained imprints from 14 cases showed a composite tumor population mainly consisting of histiocyte-appearing cells, poorly differentiated atypical cells, and multinucleated giant cells. These cells, irrespective of cytologic features, revealed a diffuse, moderately to strongly positive reaction with acid phosphatase and nonspecific esterase. Naphthol-AS-D-chloroacetate esterase, Sudan black B, alkaline phosphatase, and beta-glucuronidase reactions were completely negative. Immunoperoxidase studies in 11 cases demonstrated that tumor cells stained positively for both kappa and lambda chains. These cells were also positive for albumin. Polytypic staining for IgG was observed in two cases, and a weak staining for lysozyme was found in two other nodes. Global results confirm the value of these studies for functional profile determination of MH proliferating cells. A combined approach using a variety of cytochemical and immunohistochemical techniques should be routinely considered in MH as useful additional studies for a more precise diagnostic definition of the disease.

Adolescent↗
PubMed1984

Treatment of acute myeloid leukemia with a combination of intensive induction chemotherapy, early consolidation, splenectomy and long-term maintenance chemotherapy.

The authors developed a therapeutic regimen in which 33 patients aged 11 to 61 years (mean +/- SE, 35.9 +/- 2.3 years) with acute myeloid leukemia (AML) were given intensive induction chemotherapy with Adriamycin (doxorubicin) (ADM), vincristine (VCR) and cytosine arabinoside (ARA-C). Twenty-nine of these patients (88%) attained a complete remission (CR) after 1, 2, or 3 courses and were then subjected to an early consolidation course of chemotherapy, identical to that for induction. After consolidation, all patients in CR received a long-term continuous maintenance therapy in which 6-mercaptopurine (6-MP) and methotrexate (MTX) were alternated, associated with periodic reinforcements with daunorubicin (DNR) and VCR. Twenty-five of the 29 patients who achieved a CR were splenectomized soon after the consolidation course. Histologic sections of the spleens, liver biopsy specimens, and lymph nodes, stained routinely and with the naphthol AS-D chloroacetate esterase (NCA) method, showed mature granulocytes and a few NCA positive mononuclear cells, but no proved leukemic infiltrates. For the 25 splenectomized patients, the probability of remaining in CR at 36 and 54 months was 75% and 66%, respectively; the probability of survival at 36 and 54 months was 85% and 75%, respectively. Age older than 40 years and evidence of extramedullary involvement at presentation appeared to carry a bad prognosis for disease-free survival.

Acute Disease↗
PubMed1984

On the histogenesis of Ewing's sarcoma. An ultrastructural, immunohistochemical, and cytochemical study.

Forty-two cases of Ewing's sarcoma (ES) have been studied with light microscopy during the 9-year period 1974 to 1982. Thirty-three patients had ES of bone, and in 9 patients the tumor was located in the extraskeletal soft tissues. Cases which fulfilled all the morphologic criteria were accepted as typical ES (31 cases), and those with some architectural or cytologic peculiarities were considered atypical forms of ES (11 cases). An immunohistochemical study (PAP method) to evaluate the presence in the tumor cells of the following markers: myoglobin, F-VIII-related antigen, lysozyme, alpha-1-antitrypsin, alpha-1-antichymotrypsin, and immunoglobulins (IgG, IgA, IgM, kappa and lambda light chains), was performed with negative results in all cases (paraffin blocks were available in 38 cases). The cytochemical study on fresh tissue imprints from five patients (PAS, Sudan Black, alpha-naphthyl acetate esterase, acid phosphatase, beta glucuronidase, myeloperoxidases, naphthol-AS-D chloroacetate esterase and alkaline phosphatase) gave no pattern of histogenetic significance, PAS being the best morphologic marker in tissue sections and touch preparations. A detailed ultrastructural study was performed on 34 cases; the main findings may be summarized as follows: medium sized cells, polygonal shape, oval nuclei, smooth nuclear envelope, abundant euchromatin, well-developed nucleolonema, scant membranous organelles, abundant hyaloplasmic glycogen, occasional lipid vacuoles, straight cell membranes, and primitive intercellular junctions. No differences were found between bone and extraskeletal ES; moreover, typical and atypical forms showed moderate quantitative differences with no qualitative change. The histogenesis is discussed; no functional or morphologic markers have been found to suggest the cell of origin; however, some cell lines may be excluded. It is the impression of the authors that they are dealing with a primitive noncommitted mesenchymal cell.

Adolescent↗
PubMed1984

ARH-77, an established human IgG-producing myeloma cell line. I. Morphology, B-cell phenotypic marker profile, and expression of Epstein-Barr virus.

Monolayer cultures of ARH-77 cells, a human myeloma cell line propagated in vitro, display a variety of morphologic entities ranging from small lymphocytes to classic plasma cells. The cells show intense pyronin and periodic acid-Schiff affinity but are negative for colloidal iron, sudan black, and naphtol AS-D chloroacetate esterase. The cells exhibit phenotypic markers pertaining to each stage of the B-cell lineage. They fail to display sheep erythrocyte and bovine erythrocyte-IgG antibody complex rosettes, common acute lymphocytic leukemia (ALL) antigens and T-cell antigens, but most cells display surface complement receptors, Ia-like antigens, and surface and intracytoplasmic Ig. Monoclonal antibodies were negative for T-antigens, myelomonocytic cell antigens, leukemia-associated antigens, and BA-1 and OKT-10 antigens. However, 100% of the cells were positive with OKT-9 and B3/25 antibodies that are specific for transferrin receptors. About 50% to 80% of the cells were positive for surface membrane immunoglobulin (kappa IgG) and about 10% to 50% for cytoplasmic immunoglobulin (kappa IgG). Virtually all cells were positive when tested for nuclear Epstein-Barr virus antigens.

Adult↗
PubMed1986

Biphenotypic lymphoblastic lymphoma. An unusual tumor with lymphocytic and granulocytic differentiation.

An unusual example of a lymphoblastic lymphoma with evidence of both T-lymphocytic (Leu-1, Leu-2, Leu-3, OKT-6, terminal transferase-positive) and immature granulocytic (Mo1, chloroacetate esterase, lysozyme, alpha-1-antitrypsin-positive) cell proliferations was studied. The tumor arose in the oropharynx of a 39-year-old man without evidence of blood or bone marrow involvement. This tumor has been termed a "biphenotypic lymphoblastic lymphoma," and the origin of which appears to be from uncommitted progenitor cells capable of both lymphoid and myeloid differentiation. Biphenotypic lymphoblastic lymphomas, like biphenotypic leukemias, may occur more commonly than is appreciated, and may account for reported cases of acute myeloblastic leukemia after lymphoblastic lymphoma.

Adult↗
PubMed1986

Lineage ambiguity in acute leukemia.

Two cases of acute nonlymphocytic leukemia that showed surface phenotypes characteristic of lymphoid cells are reported. The cases, both involving female patients were studied by a variety of methods including flow cytometry and karyotyping. In Case 1, the patient, a 10-year-old girl, had poorly differentiated myeloblasts (FAB M1), which were weakly positive for Sudan black B (SBB), but negative for alpha naphthyl acetate esterase (NAE) and naphthol ASD chloroacetate esterase (CAE). Myeloperoxidase was demonstrated ultrastructurally in some of the blasts. In Case 2, the 30-year-old patient had typical myelomonocytic leukemia (FAB M4), with SBB-, NAE-, and CAE-positive blasts. Both cases were negative for terminal deoxynucleotidyl transferase. Case 1 was negative for myeloid membrane markers, whereas Case 2 was strongly positive for My7 and My9. Surprisingly, both cases showed significant positivity for B-cell restricted antigens B1, B2, and B4. These findings suggest ambiguous or dual lineage, supporting the concepts that some leukemias could arise from a pluripotent hematopoietic progenitor cell (Case 1) or from cells that though differentiated in some respects, could still preserve some early antigens (Case 2).

Acute Disease↗
PubMed1986

Granulocytic sarcoma in nonleukemic patients.

Sixteen patients presenting with granulocytic sarcoma without evidence of acute leukemia were seen and diagnosed at The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston from 1962 to 1985. Seven of them (44%) did not develop acute leukemia. Of these seven, four are alive with no evidence of disease 3.5 to 16 years after initial presentation; the remaining three patients died of their disease within 2 to 8 months of presentation. Two of 16 patients were diagnosed within the last 15 months and do not have adequate follow-up. The seven remaining patients developed acute leukemia within 1 week to 13 months of the diagnosis of granulocytic sarcoma. Six of them died 5 weeks to 16 months after diagnosis; one patient has been in complete remission for 8 years. Twelve of these 16 cases (75%) were initially misdiagnosed, most frequently as large cell lymphoma. The remaining four cases were correctly diagnosed as granulocytic sarcoma. The naphthol-ASD-chloroacetate esterase stain was required to make the correct diagnosis in all cases. Contrary to findings in other series, granulocytic sarcoma arising in nonleukemic patients does not necessarily progress to acute leukemia. At least four of 16 (25%) patients in this series did not develop acute leukemia during the 3.5 to 16 years they have been followed. No prognostic factors were identified in this series to predict which patients would develop acute leukemia and which ones would not.

Adolescent↗
PubMed1987

Megakaryoblastic transformation of chronic granulocytic leukemia.

Three cases of megakaryoblastic transformation of chronic granulocytic leukemia (CGL) are reported. In each case, the leukemic transformation had morphologic features suggesting megakaryocytic differentiation. This was confirmed by positive immunostaining with a monoclonal antibody (HP1-1D) specific for platelet and megakaryocyte glycoprotein IIb/IIIa antigen, which was expressed by the majority of the leukemic blasts in all three cases. Cases with evidence of multilineage differentiation of the leukemic transformation were excluded. A striking feature in two patients was the manifestation of lytic bone lesions and soft tissue masses at presentation. A biopsy of a lytic bone lesion and soft tissue mass in one patient revealed a megakaryoblastic leukemic infiltrate, which by immunocytochemical staining was positive for the megakaryocytic markers, glycoprotein IIb/IIIa antigen, and Factor VIII (von Willebrand factor) antigen. In contrast to granulocytic sarcomas, the megakaryoblastic sarcoma did not stain cytochemically for chloroacetate esterase. The mean survival after acute transformation was 5.3 months. The three cases of megakaryoblastic transformation represented a significant proportion of all CGL blastic transformation cases (ten cases) evaluated by bone marrow examination in our institution during a 13-month period. Megakaryoblastic transformation of CGL may occur more frequently than has been appreciated, and can present as lytic bone lesions or as soft tissue megakaryoblastic sarcomas.

Adult↗
PubMed1987

Granulocytic sarcoma presenting as pulmonary nodules and lymphadenopathy.

A patient presented with anterior and posterior cervical lymphadenopathy as well as widespread intrapulmonary nodules. Histologic sections of both lymph node and lung revealed dense infiltration by sheets of cells which were cytochemically positive for chloroacetate esterase and myeloperoxidase, thus suggesting a diagnosis of granulocytic sarcoma. The patient was initially treated with daily hydroxyurea. After 6 weeks, when progression of the disease was apparent, hydroxyurea was discontinued and the patient was placed on mithramycin, an agent reported to induce differentiation of myeloid precursor cells both in vitro and in vivo. On this latter agent, a dramatic response has been noted with a decrease in the pulmonary symptoms, and a marked reduction in the size of the lymph nodes and lung nodules. The authors report this case because it represents a rare presentation of an uncommon disease and because of the striking improvement that followed the initiation of a novel therapeutic modality.

Aged↗
PubMed1989

Liver findings in generalized mastocytosis. A clinicopathologic study.

Although the liver is one of the four organs most often involved in generalized mastocytosis (GM), little is known about macroscopic and microscopic liver findings in this rare disease. This study included 182 patients with GM (confirmed in most by bone marrow histologic study), comprising 52 cases of our own and 130 reported in the literature. Hepatomegaly was found in 131 (72%) of the 182 patients, cirrhosis in seven (4%), and periportal fibrosis in 25 (14%). Mast cell (MC) infiltration of the liver was confirmed histologically in 77 (42%). Liver specimens were available for further histologic investigation in 11 of our own cases of GM. Nine of these contained MC aggregates. Mast cells were found predominantly in the portal tracts but numerous MC also were loosely scattered throughout the sinusoids. Diagnostic confusion of GM with reactive lesions of the liver is unlikely to occur since MC, according to our own observations and the available literature, are found only in very low numbers in normal liver tissue, where they occur mainly in the portal tracts. Reliable identification of MC does, however, require special stains, like Giemsa, toluidine blue, or naphthol AS-D chloroacetate esterase.

Adult↗
PubMed1989

Acute myelogenous leukemia with leukemia cutis. Eighteen cases seen between 1969 and 1986.

Leukemia cutis was documented by biopsy in 18 of 877 patients (2%) with acute myelogenous leukemia (AML) seen at Roswell Park Memorial Institute (Buffalo, NY) between 1969 and 1986. French-American-British (FAB) types included four M2, one M3, ten M4, and three M5. Lysozyme was more consistently detectable in skin sections in our cases than Leu-M1, alpha-1-antitrypsin, alpha-1-antichymotrypsin, or chloroacetate esterase activity. Additional extramedullary sites of involvement were present in 16 patients, including meningeal leukemia in six. Two patients had leukemia cutis preceding bone marrow leukemia. Skin was the initial site of relapse in 11 patients, without marrow relapse, occurring as late as 5.5 years after diagnosis. Most patients in this retrospective series were treated with radiation therapy and/or palliative chemotherapy, and did poorly, with prompt bone marrow relapses and serial skin relapses. Long-term disease-free survival was achieved in the one patient whose skin relapse was treated with whole-body electron-beam radiation therapy in conjunction with reinduction and consolidation chemotherapy. Severe skin toxicity was caused by administration of Adriamycin (doxorubicin) 12 days after electron-beam irradiation in one patient, but was not seen when cytosine arabinoside was administered in doses up to 3 g/m2 in conjunction with radiation therapy. This retrospective review suggests that optimal management of AML involving skin might include whole-body electron-beam irradiation in conjunction with induction or reinduction chemotherapy without anthracyclines, followed by consolidation chemotherapy. Additionally, there should be ongoing surveillance for and treatment of extramedullary disease at other sites, including the meninges.

Antigens, Differentiation, Myelomonocytic↗
PubMed1991

Congenital angiotropic lymphoma (intravascular lymphomatosis) of the T-cell type.

The autopsy of a stillborn infant showed an extensive intravascular proliferation of atypical cells throughout the body. There was no infiltration by these cells of the parenchyma of the bone marrow, lymph nodes, or thymus. By histochemistry, these cells were negative for naphthol-ASD-chloroacetate esterase, a marker of granulocytes. By immunohistochemistry, they were reactive with MT-1 and anti-Leu-22, but unreactive with MB-1, L26, anti-Leu-M1, Tü-9, and antihemoglobin antibodies. A few cells reacted with antileukocyte common antigen and UCHL-1. Based on these findings, the lesion was diagnosed as angiotropic lymphoma (intravascular lymphomatosis) of the T-cell type, which occurred congenitally. Most angiotropic lymphomas in the literature are of the B-cell type, and no leukemia virus type I antibody was negative in the mother.

Female↗
PubMed1994

Functional characteristics of in vivo induced neutrophils after differentiation therapy of acute promyelocytic leukemia with all-trans-retinoic acid.

The authors describe the functional capabilities of in vivo induced neutrophils from a patient with acute promyelocytic leukemia (French-American-British M3v) treated with differentiation therapy using all-trans-retinoic acid (45 mg.m-2.day-1). The induced neutrophils from the leukemic clone appeared in the blood 7 days after therapy. Normal neutrophils, presumably derived from nonclonal normal hematopoiesis, appeared 15 days after the initiation of therapy. The induced neutrophils were separated from normal neutrophils by density gradient centrifugation. Their origin was established by fluorescence in situ hybridization. The induced neutrophils were morphologically atypical but stained for myeloperoxidase (Sudan black B) and AS-D chloroacetate esterase and were negative for alpha-naphthyl butyrate esterase. Induced neutrophils were functionally mature, showing nitroblue tetrazolium reduction in 72% of the cells compared with 84% in the normal neutrophil fraction. Both the rate and total killing of Staphylococcus aureus (American Type Culture Collection Strain 25923) were normal in both neutrophil fractions. Random locomotion was equivalent and within the normal reference range in both fractions; however, using the under-agarose technique, induced neutrophils showed a minor chemotactic defect in response to both n-formyl-methionyl-leucyl-phenylalanine (score 292, normal 338-868) and complement-derived chemotactic factors (score 420, normal 457-1408). At autopsy, induced neutrophils infiltrated necrotic myocardial tissue, suggesting a normal response to inflammatory stimuli.

Adult↗
PubMed2000

Total synthesis of the antitumor antibiotic (+/-)-fredericamycin A by a linear approach.

A linear approach to the total synthesis of racemic fredericamycin A (1) through the oxidative intramolecular [4 + 2] cycloaddition of a (phenylthio)acetylene-cobalt complex is described, which is applicable for the asymmetric total synthesis of naturally occuring 1. The highlight of this work is the aromatic Pummerer-type reaction with 1-ethoxyvinyl chloroacetate, which effects the introduction of the oxygen functional group to the internal B-ring of the highly functionalized, congested polyaromatic ABC-ring moiety.

Antibiotics, Antineoplastic↗
PubMed2001

Resolution in capillary electrophoresis with nonaqueous methanol as solvent: theoretical prediction and experimental confirmation.

The resolution of the analytes was predicted from their known pKa* values and actual mobilities in nonaqueous methanolic solutions according to theory taking longitudinal diffusion as the only cause for peak dispersion. This leads to an equation of the resolution as a function of the pH*, as both selectivity and efficiency are dependent on the pH of the buffer. The experimentally obtained resolution values were in acceptable agreement with the predicted theoretical ones in most cases. This was demonstrated for substituted benzoic acids as analytes. The pKa* values needed for the calculation of the resolution were derived from the pH* dependence of the effective mobility. The pH* scale in methanol was based on conventional pKa* values of acetic acid and chloroacetic acid taken from the literature.

Benzoates↗
PubMed1977

Cytochemical "normal" and "abnormal" eosinophils in acute leukemias.

Eosinophilic leukocytes may accompany a great variety of disorders and different types of acute leukemias. The most striking morphologic feature of eosinophils is their specific granules, but morphology alone often is insufficient to differentiate normal from abnormal eosinophils. Cytochemically, the eosinophils were considered "normal" when they did not contain alkaline phosphatase, chloroacetate esterase, toluidine blue metachromasia, Astra blue positivity, and specific PAS-positive granules, but did have peroxidase and cyanide-resistant peroxidase activities, Sudan black positivity and moderate naphthol-AS esterase or alpha-naphthyl esterase and acid phosphatase positivities. In seven cases of acute leukemias (two acute myeloblastic and five myelomonocytic), in contrast with their normal behaviour, the eosinophils show "abnormal" cytochemical positivities consisting of chloroesterase activity, PAS and Astra blue positivities of the specific granules, toluidine blue metachromasia, and cyanide-resistant peroxidase of a few specific granules. Cytochemical investigations may provide additional criteria for evaluating the abnormality of the eosinophilic cell in leukemias.

Adult↗
PubMed1983

Studies on abnormal polymorphonuclear neutrophils in acute myelogenous leukemia: clinical significance and changes after chemotherapy.

In patients with acute myelogenous leukemia (AML), 34 out of 35 patients (97%) had cytochemically abnormal polymorphonuclear neutrophils (PMN). Some interesting regularity was noted in the appearance of cytochemical abnormalities of the PMNs. When peroxidase (PO) activity was low, both alkaline phosphatase (AP) and chloroacetate esterase (CAE) activities were also low (group A). When PO activity was normal, if AP activity was low, CAE activity tended to be high (group B) and if AP activity was high, CAE activity tended to be low (group C). Complete remission rate of group B (65%) seemed to be better than that of group C (20%) and group A (25%) although the differences was not statistically significant. In these patients, the number of peripheral leukemic blasts and PMNs showed a significant positive correlation (r = 0.69, p less than 0.005). Furthermore, patients with higher circulating PMN counts (more than 2 X 10(9)/L) had a significantly worse prognosis than patients with lower counts (p less than 0.05). These rather unexpected findings strongly suggest that cytochemically abnormal PMNs are progeny of AML blasts. The change in the proportion of abnormal PMNs associated with chemotherapy were studied in 21 patients during the remission induction period. Abnormal PMNs disappeared from the circulation in patients who achieved complete remission. In contrast, abnormal PMNs persisted throughout the remission induction period in patients who failed to achieve complete remission.

Alkaline Phosphatase↗