Acute leukemia and the transient myeloproliferative disorder associated with Down syndrome: morphologic, immunophenotypic and cytogenetic manifestations.

Individuals with Down syndrome have an increased incidence of leukemia compared to the general population. In addition, Down syndrome children may acquire a myeloproliferation that resembles acute leukemia that undergoes a spontaneous, durable remission. To clarify the relationship between these two disorders, the morphologic, immunophenotypic and cytogenetic characteristics of 28 patients with Down syndrome and the morphologic manifestations of acute leukemia were examined. Three cytomorphological groups were discerned. The first two groups consisted of five patients with acute lymphoblastic leukemia (group I) and three patients with acute myeloid leukemia (group II). These leukemias resembled those of non-Down individuals. The third and largest group (group III) consisted of 20 cases of acute myeloid leukemia that showed prominent megakaryocytic and/or erythroid differentiation and occurred in children under 6 years of age. The blasts in this group were non-reactive for myeloperoxidase or non-specific esterase and expressed CD7, CD34 and CD36 with variable expression of CD61, CD13 and CD33. Four patients in this group had an acquired trisomy 8. Four group III leukemias underwent a durable, spontaneous remission within 2 months of diagnosis. There were no morphologic differences between those leukemias in this group that progressed and those that remitted; however, all remissions occurred in newborns. It is concluded that Down syndrome children acquire a characteristic acute myeloid leukemia that has prominent megakaryocytic and/or erythroid differentiation and an unusual immunophenotype. This group of leukemias may undergo a durable, spontaneous remission in the newborn period.

S100-positive, T-cell chronic lymphoproliferative disease: an aggressive disorder of an uncommon T-cell subset.

S100-positive T lymphocytes account for less than 3% of peripheral blood T cells. Rare cases of S100-positive T-cell lymphoma have been previously described. We report four such cases of S100-positive T-cell chronic lymphoproliferative disease. In all cases, hepatosplenomegaly was observed, without prominent lymphadenopathy. Central nervous system (CNS) involvement by the leukemic cells was suggested in three cases by physical symptoms and confirmed in two cases by cerebrospinal fluid studies. Despite treatment, three patients died at 3, 6, and 8 months after diagnosis. Although there was a leukemic presentation, only minimal bone marrow infiltration was evident. Splenectomy showed red pulp infiltration. Liver and lymph node biopsies showed sinusoidal leukemic involvement. In all cases, the leukemic cells expressed mature T-cell- and natural killer cell-associated antigens. Cytoplasmic S100 was detected in the leukemic cells in the blood, spleen, liver, and lymph node. Southern blot studies in two cases showed T-beta, T-gamma, and T-delta gene rearrangements. RNA Northern blots showed T-alpha and T-beta chain transcripts with no T-gamma or T-delta RNA identified. Southern blot analysis showed no hybridization to probes specific for Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus-1, or human T-cell lymphotropic virus type-1. These findings show that S100-positive T-cell chronic lymphoproliferative disorder is an aggressive, extramedullary-based disease frequently associated with CNS involvement and characterized by short survivals.

Detecting fetomaternal hemorrhage: a comparison of five methods.

Appropriate postpartum administration of Rh immune globulin relies on sensitive detection and accurate quantitation of fetomaternal hemorrhage (FMH). Recently, the microscopic Du test (micro Du) enhanced with polyethylene glycol (PEG Du) and flow cytometry (FC) have been advocated for this purpose. Three qualitative methods (micro Du, rosette test, and PEG Du) and two quantitative methods (acid elution and FC) for assessing FMH were evaluated with particular attention given to PEG Du and FC. In vitro studies comprised 10 series of dilutions of D+ cord cells in D- adult cells to yield D+ cell concentrations of 0.06, 0.12, 0.25, 0.50, 0.75, 1.0, and 2.0 percent. Additionally, 26 postpartum samples were tested. Of the qualitative techniques, the micro Du test was the least sensitive with 20 percent false-negative results occurring at 0.5 percent fetal cells. The PEG Du test was only slightly more sensitive and offered no clinical advantage. The rosette test was the most sensitive, consistently detecting fetal cells at concentrations of 0.25 percent or greater. FC and acid elution showed similar results, with good correlation obtained between measured and expected quantities of fetal cells (r = 0.99 and 0.96, respectively). One of 26 postpartum samples was positive by all screening techniques; acid elution and FC detected 0.3-percent concentrations of fetal cells and 0.17-percent concentrations of D+ cells, respectively. Although acid elution is a more commonly used method for quantitating FMH, FC offers an acceptable alternative that is capable of analyzing large numbers of cells with objectivity and reproducibility.

Eosinophilic leukemia: a myeloproliferative disorder distinct from the hypereosinophilic syndrome.

Evidence to support the existence of eosinophilic leukemia (EL) as an autonomous eosinophilic proliferation analogous to other myeloproliferative disorders has been somewhat confusing. Partially obscuring the existence of EL as a distinct entity is the proposal that EL merely represents a clinically aggressive form of hypereosinophilic syndrome. This report details the clinical and pathologic findings in a case of EL. The presence of trisomy 8 and trisomy 21; morphologic, cytochemical, and ultrastructural findings of granular abnormalities and nuclear/cytoplasmic dysynchrony; and a clinical course similar to that of other myeloproliferative disorders support the existence of EL as a rare but distinct entity within the spectrum of myeloproliferative diseases.

A case of large cell CNS lymphoma associated with a systemic small cell lymphocytic lymphoma.

A case is reported of a 59 y/o woman with a large cell CNS lymphoma and a small cell lymphocytic lymphoma in the bone marrow. The brain tumor underwent spontaneous regression and subsequent regrowth while there was slow progression of the systemic small cell lymphoma. The CNS lymphoma regressed rapidly following treatment with prednisone and cyclophosphamide. We hypothesize that the small cell lymphoma in this patient may represent an underlying immunodeficiency disorder.

Plasma cell leukemia and hyperviscosity syndrome.

A 56-year-old man had dyspnea, weight loss, hemoptysis, and a generalized bleeding diathesis. Physical examination disclosed hepatosplenomegaly, congestive heart failure, and multiple sites of bleeding. Severe anemia, thrombocytopenia, rouleaux formation, and a leukocytosis with circulating immature plasma cells were observed, along with azotemia, hyperuricemia, and marked elevation of total proteins with a monoclonal IgG kappa spike. The finding of increased serum viscosity confirmed the clinical impression of the hyperviscosity syndrome. Emergency plasma exchange produced marked improvement in the clinical manifestations of hyperviscosity syndrome. Systemic chemotherapy resulted in a partial remission of the disease, but the patient ultimately died of complications of treatment. In this review, we discuss the diagnosis and management of the hyperviscosity syndrome.

Richter's syndrome presenting as primary central nervous system lymphoma. Transformation of an identical clone.

The development of a central nervous system (CNS) large cell lymphoma in a patient simultaneously diagnosed with chronic lymphocytic leukemia (CLL) is reported. Although differences in phenotypic expression were demonstrated in study of the peripheral blood and CNS disease, identical immunoglobulin gene rearrangements were identified, providing evidence for evolution of two morphologically distinct neoplasms from the same clone. Beyond histologic transformation, acquisition of an aneuploid cell population in the CNS tumor was demonstrated by analysis of DNA content. Isolated parenchymal involvement of the CNS by large cell transformation of CLL has not been previously described; its relationship to CNS lymphoma and Richter's syndrome are reviewed.

T-cell non-Hodgkin lymphoma in human immunodeficiency virus-1-infected individuals.

We present two patients with human immunodeficiency virus-1 (HIV-1) infection in whom T-cell non-Hodgkin lymphoma developed, based on pathologic diagnosis, immunophenotyping, and T-cell receptor gene rearrangement. Both cases were positive for human immunodeficiency virus-1 by enzyme-linked immunosorbent assay and immunoblot methods. Histologic sections from each patient showed a high-grade pleomorphic T-cell non-Hodgkin lymphoma, and immunophenotyping demonstrated a prevalence of reactivity for CD4 (helper) over CD8 (suppressor) antigens. T-cell receptor beta-chain gene rearrangement studies revealed a rearranged pattern with either the HindIII or BamHI enzymes, whereas immunoglobulin heavy chain genes retained a germ-line configuration. Viral sequences specific for human T-cell leukemia virus-I, human T-cell leukemia virus-II, or HIV-1 were not detected. Thus, although rare, T-cell non-Hodgkin lymphoma may be observed in HIV-1-infected individuals.

Glycohemoglobin quantitation by alkaline gel electrophoresis. A reliable technique with practical clinical advantages.

The Beckman Paragon alkaline gel electrophoresis system was evaluated for utility in identification and quantitation of glycosylated hemoglobin in the clinical laboratory setting. In contrast to other alkaline hemoglobin electrophoresis systems, this system provides adequate separation of HbA0 from its glycosylated form. A band anodal to HbA0 was identified as glycohemoglobin; in vitro synthesis of glycohemoglobin confirmed the migration pattern of the glycohemoglobin band. In both in vitro synthesis studies and in a series of 48 patients, quantitation of the glycohemoglobin band by densitometry showed good correlation (r = 0.99 and r = 0.96, respectively) with values obtained by a standard column chromatographic technique. Beyond reliable quantitation of glycohemoglobin, this system offers two advantages. First, it discriminates hemoglobin F and hemoglobins with low isoelectric points that may coincidentally be measured as glycohemoglobin by other techniques. Second, it provides simultaneous detection of common hemoglobinopathies, a necessity for accurate reporting of glycohemoglobin in the diabetic patient with a concomitant hemoglobinopathy.

Primary lymph node presentation of angiocentric lymphoma associated with features of a hemophagocytic syndrome.

The spectrum of post-thymic T-cell neoplasia includes the angiocentric immunoproliferative lesions, a group of disorders histologically exhibiting vascular infiltration and destruction; included among these disorders is angiocentric lymphoma. In contrast to the typical extranodal presentation seen in the angiocentric immunoproliferative lesions, this report describes a case of angiocentric lymphoma presenting as primary lymph node disease with clinicopathologic findings mimicking a hemophagocytic syndrome. Rearrangement of the T-cell receptor beta chain documents this case to be a clonal T-cell neoplasm. The association of this distinct histologic type of T-cell malignancy with hemophagocytic syndromes is reviewed.

Systemic polyclonal immunoblastic proliferations.

This report describes the clinical and pathologic features of four patients with a florid, systemic immunoblastic proliferation. The blood of these patients exhibited a mild to marked leukocytosis with a high percentage of immunoblasts and plasma cells. The bone marrow also was infiltrated extensively by immunoblasts. Lymph node biopsy specimens from two patients showed near total effacement of the nodal architecture by a diffuse infiltration of immunoblasts and plasma cells. The proliferative process was determined to be polyclonal with immunohistochemical techniques. Cytogenetic studies of bone marrow from two patients showed a pseudodiploid abnormal clone, with a translocation involving a break in band 14q32 in each case. The pathogenesis of these proliferative disorders in unclear, although three patients had some evidence of an acute immune disorder. One of these patients was treated with steroids, vincristine, and cyclophosphamide. Another patient was treated with steroids only, and one patient was treated with steroids and cyclophosphamide. All had rapid regression of the disease process. Two patients are alive and apparently free of disease 31 and 48 months after diagnosis. One died of sepsis. The fourth patient had acquired immune deficiency syndrome (AIDS) and died without therapy. The biology of the immunoblastic proliferation of these patients is uncertain. The immunohistochemical results suggest a reactive, polyclonal proliferation, but the cytogenetic abnormalities in two patients indicate the possibility of a cryptic neoplastic clone.

Argyrophilic, 'carcinoid-like' prostatic carcinoma. An immunocytochemical study.

Four cases of argyrophilic or carcinoid-like prostatic carcinoma were studied immunocytochemically, using immunoperoxidase stains for prostatic-specific antigen, neuron-specific enolase, hydroxytryptamine (serotonin), somatostatin, and adrenocorticotropic hormone. All four showed strong positive reaction to prostatic-specific antigen and uniformly negative results with neuron-specific enolase, hydroxytryptamine, somatostatin, and adrenocorticotropic hormone. These findings lend further support to the concept that this particular prostatic tumor is truly a carcinoma that somehow manifests a carcinoid-like histomorphology, but does not possess evidence of true neuroendocrine or carcinoidal nature.