Prostate cancer risk assessment program. A model for the early detection of prostate cancer.

Prostate cancer is the most common form of cancer (except skin cancer) in men. Several factors have been associated with an increased risk for prostate cancer, including age, ethnicity, family history, lifestyle, and environmental exposures. Recognition of the importance of the interaction of these factors in prostate cancer has led to an interest in their evaluation as a model both for studying genetic susceptibility patterns and for studying and providing educational tools and preventive interventions. One such model has been developed at Fox Chase Cancer Center. Critical to the implementation of the model has been the establishment of the Prostate Cancer Risk Registry (PCRR) and Prostate Cancer Risk Assessment Program (PRAP). Together, they serve as a unique resource for investigating the interaction between environmental factors and genetic susceptibility patterns; exploring the early, premalignant biological markers of prostate cancer; and prospectively assessing the quality of life (QOL) of men at risk. In addition, PRAP facilitates the evaluation of models for prostate cancer risk counseling and screening in the community. This paper describes this model for early detection and risk reduction, along with preliminary data from its first two study aims. The program is particularly relevant in view of the wealth of genetic information emerging from the Human Genome Project.

Management of mania in the elderly: an update.

Manic syndromes in the geriatric population present special issues in management. The authors review the state of the art, with particular emphasis on assessment and pharmacotherapy. Research needs are emphasized.

Passive inhalation of free-base cocaine ('crack') smoke by infants.

Cocaine is one of the most widely abused substances in the United States, in part due to the availability of its inexpensive alkaloidal free-base form, "crack". A variety of medical complications, including sudden death, are known to occur in the adult-user population, regardless of the route of cocaine administration. We report 16 cases of infant death registered by the Philadelphia (Pa) Medical Examiner's Office over a 2-year period (1987 through 1989), where toxicologic analyses revealed the presence of cocaine and/or its metabolite, benzoylecgonine. Scene investigation documented that these infants, shortly before death, had been exposed to environments that contained the smoke from crack. We conclude that the route of cocaine administration in this infant population was the passive inhalation of crack smoke. It is possible that the cocaine may have contributed to the death of these infants. Thus, in addition to the adult users, infants and children exposed to environments where crack is smoked may inhale cocaine and potentially suffer from its adverse effects.

Hypernatremia due to amniotic fluid embolism during a saline-induced abortion.

A case of fatal amniotic fluid embolism leading to hypernatremia during a hypertonic saline-induced abortion is reported. This sequence of events has not, to our knowledge, been previously reported. Hypernatremia as a diagnostic aid for amniotic fluid embolism is discussed.

PIP: A case of fatal amniotic fluid embolism leading to hypernatremia following instillation of hypertonic saline is reported. This complication of saline-induced abortion has not been reported previously in the literature. The patient was an obese 16-year-old black female, gravida 1, para 0, whose gestational age at time of abortion was 21.5 weeks. 26 hours after the procedure, which was well tolerated by the patient, she complained of severe abdominal cramps with projectile expulsion of amniotic fluid. Generalized convulsions and shaking followed and the patient went into shock. Death occurred within 2 hours. At autopsy, microscopic examination of lungs revealed pulmonary edema with marked vascular congestion, focal areas of atelectasis, and intra-alveolar hemorrhages. Positive test results for mucin in a few pulmonary vessels and intra-alveolar capillaries confirmed a diagnosis of amniotic fluid embolism. There was marked congestion of the blood vessels of the kidneys, liver, brain, and spleen. Amniotic fluid embolism represents about 10% of the maternal mortality in the US; however, this complication generally occurs during labor, delivery, and the immediate postpartum period. Moreover, most such cases occur in older, multiparous women in the 3rd trimester of pregnancy. It is possible that hypernatremia following amniotic fluid embolism occurs more frequently than reported. Routine examination of blood during pregnancy and of the vitreous humor in cases of pregnancy-related mortality could be useful in establishing a diagnosis of amniotic fluid embolism.

Spontaneous rupture of the spleen due to acquired immunodeficiency syndrome in an intravenous drug abuser.

A case of spontaneous rupture of the spleen is described in a 25-year-old woman with a history of intravenous drug abuse. At autopsy the spleen and the lymph nodes were soft, slightly enlarged, and markedly congested. They showed reactive follicular hyperplasia with increased cellularity and prominent vascularity of the red pulp and the interfollicular tissue. The postmortem serum was positive for antibodies to human T-cell lymphotropic virus type III. Other serologic tests were negative, including heterophile antibody test, test for antibodies to Epstein-Barr virus, and toxoplasmosis.

B-cell lymphomas morphologically resembling T-cell lymphomas.

Seven cases of B-cell lymphoma that morphologically resembled T-cell lymphoma are described. These cases are of four morphologic types: atypical poorly differentiated lymphocytic lymphoma (PDLL) with convoluted nuclei, "Lennert's" lymphoma, mixed lymphocytic-"histiocytic" lymphoma with large variation in size of abnormal cells, and "histiocytic" lymphoma with large multilobed nuclei. These cases add further support to the belief that morphologic criteria alone are not sufficient for accurate immunologic classification of the malignant lymphomas since they may represent a distinct clinicopathologic entity.

In vitro neutrophil-erythrocyte rosette formation mediated by a serum factor (IgG).

In vitro neutrophil-erythrocyte rosette (NER) formation occurred in the peripheral blood of an elderly man. This caused problems in cross-matching for blood transfusion initially but was resolved by performing crossmatches at 37 degrees C because this phenomenon was temperature-dependent. NER formation was independent of complement and of the type of anticoagulant used. NERs were induced using normal control cells with the patient's plasma, serum, and the IgG fraction of serum. The rosetting factor was adsorbed by heterologous group-specific erythrocytes, but not by leukocytes. No neutrophil antibodies were identified.

Sudden infant death syndrome: measurement of total and specific serum immunoglobulin E (IgE).

Postmortem evaluation of total and specific serum immunoglobulin E (IgE) antibody levels by the paper radio immuno sorbent test (PRIST) and radio allergo sorbent test (RAST), respectively, revealed that there was no significant elevations in total circulating IgE or in specific IgE antibodies to house dust, Dermatophagoides farinae (house dust mite), Alterarnia tenuis (mold), or milk proteins for sudden infant death syndrome (SIDS) victims when compared to a control group.

True histiocytic lymphoma. A report of four cases.

Clinical, morphologic, cytochemical, immunologic, and ultrastructural features of four cases of true histiocytic lymphoma are described. The neoplastic cells were large, ranging from 20 to 45 mu in diameter with round, folded, or convoluted nuclei, and abundant eosinophilic cytoplasm. They exhibited diffuse nonspecific esterase activity. Diffuse acid phosphatase activity was present in two cases so tested. Muramidase activity was present in half of the cases. Finely granular PAS-positive material was seen in the cytoplasm. Methyl green-pyronin positivity was variable. An occasional neoplastic cell showed erythropagocytosis in one case. Malignant cells either contained no cytoplasmic immunoglobulins (three cases) or had immunoglobulins of multiple classes (one case). Surface markers were studied in two cases; they were absent in one case, and were of multiple classes in another case. Ultrastructurally the neoplastic cells had lysosomal granules in three cases so examined, and phagolysosomes, phagocytized material and residual bodies in one of three cases so studied. Patients ranged in age from 28 to 60 years. Two patients had extralymphatic tumors. Survival of more than 5 years was seen in one patient.

Natural killer and suppressor T-cell chronic lymphocytic leukemia.

A patient with low-grade lymphocytosis, splenomegaly, and neutropenia, but adequate myeloid leukogenesis, was found to have chronic lymphocytic leukemia, which represented a clonal proliferation of a distinct T-lymphocyte subset. The lymphocytes did not form E rosettes but had an OKT3+, OKT4+, OKT6+, OKT8+, OKT11+, HNK-1+, HNK-36+, OKIa1+, OKM1+ phenotype and functionally had suppressor and natural killer activity. Morphologically, they were large granular lymphocytes, which were strongly acid phosphatase positive and nonspecific esterase negative. They did not respond to mitogens, or to allogeneic cells. Initially, the spleen appeared to be the most involved organ and, judging from the high proportion of leukemic splenic lymphocytes in the S and G2/M phases of the cell cycle, was also the organ of origin of the leukemic cells. Only a few leukemic cells in the blood and bone marrow were in S and G2/M phases. After splenectomy, the lymphocyte count rose considerably and the bone marrow became progressively more infiltrated by tumor nodules. One year after diagnosis, the patient was started on chemotherapy because of progressive anemia. He responded to the chemotherapy by normalization of the hemoglobin and neutrophil count and had a moderate decrease in the bone marrow involvement and peripheral lymphocytosis.

The value of immunoperoxidase studies in the diagnosis of 2 cases of acute leukaemia.

2 cases of acute leukaemia in which the precise diagnosis was established using the immunoperoxidase technique on particle sections, a method not usually employed for acute leukaemias, are reported. Morphologically and cytochemically these cases were initially diagnosed as acute megakaryoblastic (case 1) and acute monocytic (case 2) leukaemia. Based on the immunoperoxidase studies, these diagnoses were corrected to DiGuglielmo's disease (case 1) and plasma cell leukaemia (case 2).

Comparison of circulating colony-forming cells in chronic granulocytic leukemia and leukemoid reaction.

In vitro culture studies of peripheral blood leukocytes using semi-solid media from 8 patients with chronic granulocytic leukemia (CGL) and 5 patients with granulocytic leukemoid reaction were performed. A markedly increased number of circulating colony-forming units were present in patients with CGL (mean 343 +/- 47) as opposed to those having granulocytic leukemoid reaction (mean 7.0 +/- 4). The colony size was larger in CGL than in granulocytic leukemoid reaction or in normal peripheral blood.

Acute megakaryoblastic Leukemia.

Acute megakaryoblastic leukemia is a rare and rapidly fetal disorder characterized by extensive proliferation of megakaryoblasts and atypical megakaryocytes in bone marrow and extramedullary sites, thrombocytopenia and only a few blasts in peripheral blood. Three cases of this leukemia were studied morphologically, cytochemically, and electron microscopically. The leukemia blasts varied from 10-20 mu in diameter, had coarsely reticular nuclear chromatin, and numerous cytoplasmic projections and vacuoles. Except for intense granular PAS positivity and diffuse acid phosphatase reactivity, all of the usual cytochemical stains were negative. The blasts had no specific differentiating features identifying them as megakaryoblasts even at the ultrastructural level. In such instances demonstration of platelet peroxidase will confirm the megakaryocytic origin. All three patients in this series were men and all died within 90 days. Two patients also had other malignancies.

Increased numbers of lymphocytes with single class surface immunoglobulins in reactive hyperplasia of lymphoid tissue.

Forty-seven lymph nodes and one stomach exhibiting reactive hyperplasia from 40 patients were examined by morphologic and immunologic methods. Twelve lymph nodes and one stomach from ten patients had a significantly increased number (greater than 25%) of lymphocytes, with single class surface immunoglobulins or plasma cells, and plasmacytoid lymphocytes secreting single class immunoglobulins. In three cases, a diagnosis of malignancy was subsequently made on the basis of morphological and immunological evidence of tumor in other tissue. Five patients had collagen disorders, two had a persistent unexplained hypergammaglobulinemia, and two had no recognized associated disease. The significance of an increase of B lymphocytes with single class surface immunoglobulins in these cases is presently not clear, but patients with similar findings should have extensive investigation and persistent follow-up.

Acute monocytic leukemia: a surface marker study.

Thirteen cases of acute monocytic leukemia (AMoL) were studied morphologically, cytochemically, and immunologically in an attempt to determine similarities and/or differences between acute monocytic and lymphocytic leukemias. Single class surface immunoglobulins (IgG kappa) were seen in six cases. These markers are thought to represent serum immunoglobulins attached to the leukemic monocytes via the receptors for the Fc portion of immunoglobulin and are not synthesized by the cells as is the case with B lymphocytes. Receptors for complement were also noted. It appears that surface immunoglobulins and receptors for the Fc portion of the immunoglobulin and complement, which are found on several classes of normal lymphocytes and monocytes, may also be found on leukemic monocytes. Antisera to B lymphocytes, detecting HlA-DRw antigens, also reacted with some of the leukemic monocytes.

Malignant lymphoma of small cleaved lymphocytes of the follicular mantle zone.

We describe a highly unusual lymphocytic lymphoma. It appeared to originate in the mantle zones of hyperplastic follicles that had large reactive centers. The tumor cells in the mantle zone were small lymphocytes with cleaved or very irregular nuclei. They had coarse and abundant IgM, kappa surface immunoglobulin markers, and receptors for complement. The tumor involvement was generalized at the time of discovery. The diagnosis of a malignant lymphoma was initially made with difficulty because of the presence of reactive follicular centers as well as a polyclonal hypergammaglobulinemia and large numbers of interfollicular plasma cells and plasmacytoid lymphocytes containing all classes of immunoglobulin. However, 2 yr later, the follicular centers were replaced by tumor nodules composed of lymphocytes identical in appearance and immunologic type to those seen originally. This case illustrates that not all nodular lymphomas are follicular center cell (FCC) neoplasms and that morphological transformation from small round to small cleaved lymphocytes and a corresponding increase in surface immunoglobulins may take place in the follicular mantle zone. The patient had a high titer of antibody to Epstein-Barr virus (EBV) and a poor lymphocyte response to concanavalin A, but neither the tumor cells nor the plasmacytoid lymphocytes contained EBV DNA.

Plasma fucosyltransferase as an indicator of imminent blastic crisis.

Plasma fucosyltransferase activity was evaluated as an indicator of an impending blastic transformation in 25 patients with chronic granulocytic leukemia (CGL). Fifteen age-and sex-matched controls were also studied. The level of enzyme activity was significantly higher in the plasma of patients with blastic transformation (1,630 +/- 570 units) compared with steady chronic granulocytic leukemia (509 +/- 110 units) and normal controls (354 +/- 57 units). In three patients with CGL, a rise in fucosyltransferase activity preceded any other clinical or laboratory parameter of blastic transformation by 16-20 weeks.

Sézary syndrome with a 14:14 (q12:q31) translocation.

The Sézary syndrome was diagnosed in a 71-year-old black woman with erythroderma, generalized lymphadenopathy and hepatosplenomegaly. The laboratory data revealed a white blood cell count of 65,000 mm3 with 81% lymphocytes, the majority having an indented or a cerebriform nucleus. The skin biopsy, the lymph node biopsy and immunologic surface marker studies confirmed the diagnosis of Sézary syndrome. The cytogenetic studies of the bone marrow and the peripheral blood revealed a (14:14) (q12:q31) translocation present, consistently in majority of the lymphocytes. This translocation is considered characteristic of ataxia-telangiectasia and, to our knowledge, has not been previously described in Sézary syndrome.

Lymphocytic lymphoma simulating hairy cell leukemia: a consideration of reliable and unreliable diagnostic features.

Morphologic, immunologic and functional characteristics of an unusual poorly differentiated diffuse lymphocytic lymphoma closely resembling hairy cell leukemia are presented and the diagnostic features of the latter disease are reviewed. The malignant cells morphologically resembled hairy cells at the light as well as electron microscopic level. They had surface characteristics of both T and B lymphocytes, were phagocytic, and adhered to glass. The spleen was smooth and resembled that seen in hairy cell leukemia. Although there was a predilection for the red pulp of the spleen, there was a lack of characteristic pseudosinus formation, and areas of predominantly white pulp involvement considered characteristic of lymphocytic lymphoma were found after extensive examination.