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PubMed1977

Hematopathology and Pathogenesis of the X-linked recessive lymphoproliferative syndrome.

Subtle immunodeficiency to infectious agents including measles virus and ten Epstein-Barr virus (EBV) has been described in the X-linked recessive lymphoproliferative syndrome. This syndrome has affected six male cousins and possibly another boy. Three brothers died of an infectious mononucleosis syndrome, in a maternal cousin agammaglobulinemia developed three years after infectious mononucleosis, and two half-brothers of the Duncan kindred died of lymphoma of the brain and intestinal tract, respectively. In three of the boys, unusual measles viral infections had developed. Paramyxovirus-like particles suggestive of measles virus were seen at necropsy in the atrophic lymphoid tissue of two boys. Also, numerous plasma cells were seen in the brains, visceral organs and the thymus glands, and thymic-dependent lymphocytes were sparse in lymph nodes and spleen. The abnormal lymphopoiesis in the syndrome probably results from a subtle immunodeficiency, and concurrent measles and EB virus infections.

Agammaglobulinemia↗
PubMed1993

Human ehrlichiosis: hematopathology and immunohistologic detection of Ehrlichia chaffeensis.

Human ehrlichiosis is a recently described zoonosis caused by a rickettsia that infects leukocytes. Most patients have fever, headache, chills, and myalgias and develop leukopenia, thrombocytopenia, anemia, and elevations in serum hepatic aminotransferases. The cause of the peripheral leukopenia and thrombocytopenia is not known. We studied peripheral blood smears, bone marrow aspirates, and bone marrow biopsy specimens from patients with serologically proven ehrlichiosis to characterize the pathologic changes associated with leukopenia or thrombocytopenia, to detect the presence of immunohistologically demonstrable ehrlichiae, and to establish the infected host target cell(s). Specimens were obtained from 12 patients, and immunohistology for Ehrlichia chaffeensis was performed on tissue sections, aspirated bone marrow, and peripheral blood smears. Mean leukocyte and platelet counts available for nine patients were white blood cell count 3,300/microL (range, 1,100 to 10,300/microL) and platelets 61,000/microL (range, 40,000 to 82,000/microL). Findings included myeloid hyperplasia (eight cases), megakaryocytosis (seven cases), granulomas (eight cases), marrow histiocytosis (one case), myeloid hypoplasia (one case), pancellular hypoplasia (one case), and normocellular marrow (two cases). Morulae of E chaffeensis were detected in four of 10 cases examined by immunohistology. Most ehrlichiae were detected within histiocytes, although morulae were rarely present within lymphocytes. Leukopenia, thrombocytopenia, or pancytopenia apparently most often results from peripheral sequestration or destruction; however, hypoplasia of marrow elements is present occasionally. Immunohistologic demonstration of E chaffeensis offers a direct means for establishing the etiologic diagnosis. These observations show the relatively frequent occurrence of bone marrow granulomas and suggest that infection of cells of the reticuloendothelial system may participate in the pathogenesis of human ehrlichiosis.

Adult↗
PubMed1987

Chronic radiation leukemogenesis: postnatal hematopathologic effects resulting from in-utero irradiation.

Previous studies have shown that continuous whole-body exposure to low daily doses of gamma radiation is highly leukemogenic for beagles initially exposed during either young adulthood or fetal development. In contrast, terminated radiation-exposure regimens (continuous exposure terminated after accumulation of preset total radiation doses) markedly reduce leukemogenic potential. In this study, we examined leukemic incidences and postnatal hematopoietic function in three groups of dogs; continuously irradiated (7.5 cGy/day) during both fetal life and after birth, continuously irradiated during fetal life only, and nonirradiated. Results were compared to results from studies with similarly irradiated and nonirradiated groups of young adult dogs initially tested at 400 days of age. Hematopoietic function was assessed in terms of both circulating blood levels of red cells, platelets, granulocytes, and monocytes, and marrow concentrations and radiosensitivities of hematopoietic progenitors. Results indicated that under continuous fetal/postnatal irradiation, i.e. the high leukemogenic exposure regimen, a marked, progressive suppression in hematopoietic function occurred following birth. This suppression continued to 100-150 days of age and was followed by partial hematopoietic recovery that was associated with an acquired radioresistance by hematopoietic progenitors. In contrast, neonates that had been continuously irradiated during fetal life, but not postnatally, i.e. the low leukemogenic regimen, exhibited a similar initial suppression of hematopoietic function followed by partial recovery. However, no temporally linked acquisition of radioresistance by hematopoietic progenitors was demonstrated. These results support the hypothesis, developed from earlier studies with adult dogs, that the processes of acquired radioresistance and recovery in numbers of transformable hematopoietic progenitors are causally linked to early stages of the leukemogenic process under continuous ionizing irradiation.

Animals↗
PubMed2001

Anaplastic large cell lymphoma: the shifting sands of diagnostic hematopathology.

Anaplastic large cell lymphoma (ALCL) is a paradigm for the process used to define new disease entities, and provides a model that is applicable to all areas of pathology. ALCL was first recognized based on characteristic histologic features (sinusoidal invasion) and a distinctive immunophenotype (CD30+). However, neither sinusoidal invasion nor CD30-positivity proved to be entirely specific. Subsequently, a characteristic cytogenetic abnormality was identified, the t(2;5), that led to identification of the genes involved in the translocation (NPM/ALK) and insights into the pathogenesis. Generation of monoclonal antibodies to the aberrantly expressed anaplastic large cell lymphoma kinase (ALK) such as ALK-1 can be used diagnostically, and have led to improved definition of the diagnostic entity with important clinical and prognostic implications. These studies also have clarified the relationship of ALCL to Hodgkin's disease, another lymphoid malignancy associated with CD30 expression. We have learned that the ultimate histologic spectrum of ALCL is both narrower and broader than originally believed. The small cell and lymphohistiocytic variants of ALCL are ALK-positive, and are an accepted part of the disease entity, although the neoplastic cells may appear neither large nor anaplastic. Conversely, most cases of Hodgkin's-like ALCL have proved to be more closely related to true Hodgkin's disease, and are unrelated to ALCL.

Activin Receptors↗
PubMed2005

Hematopathologic findings in chronic idiopathic myelofibrosis.

Until now scant knowledge was available about the dynamics of chronic idiopathic myelofibrosis (CIMF). However, follow-up studies are in keeping with a stepwise evolution starting with a prefibrotic (hypercellular) phase that progressively transforms into the classical fibro-osteosclerotic endstage with myeloid metaplasia. Prefibrotic CIMF is characterized by a granulocytic and megakaryocytic myeloproliferation lacking an increase in reticulin. Most conspicuous are abnormalities of megakaryopoiesis with regard to their histotopography and maturation. There is a more than 65% probability of progression from an early to advanced CIMF accompanied by increasing anemia, splenomegaly, and leuko-erythroblastosis. A significant relationship is recognizable among frequency, tortuosity, and luminal dilation of the microvessels and the extent of myelofibrosis. Quantity of CD34(+) progenitor cells in the bone marrow (BM) reveals a close association with advancement of disease (fibrosis, splenomegaly, anemia, peripheral blasts) and therefore prognosis. Cell kinetic studies show increased proliferation associated with a higher rate of apoptosis in initial (hypercellular) stages, as well as a reduced endoreduplicative activity of megakaryopoiesis and a blocked synthesis phase of the erythroid precursors. It is noteworthy that prefibrotic and early CIMF often present with a marked thrombocytosis mimicking essential thrombocythemia. Regarding prognosis, early CIMF is associated with a significantly more favorable survival than advanced stages.

Antigens, CD34↗
PubMed1998

Urticaria pigmentosa: a clinical, hematopathologic, and serologic study of 30 adults.

Urticaria pigmentosa (UP) is the most common form of cutaneous mastocytosis and may be associated with systemic involvement, most often of the bone marrow. The incidence of systemic involvement is not yet well established, however. To address this question, we subjected a group of 30 adults with histologically proved UP to a retrospective study that included history, physical examination, laboratory tests including cytokine measurements, radiologic examinations, and bone marrow biopsies. The most frequently associated clinical symptoms were recurrent flush episodes in 16 of 30 patients, alcohol intolerance in 13, pruritus in 10, and gastrointestinal problems in 11 (recurrent diarrhea, 8 patients; gastritis, 2 patients; and history of peptic ulcer, 1 patient). Of the 30 patients, 18 (60%) had mast cell infiltrates of the bone marrow (nodular type, 10 patients; diffuse interstitial type, 8 patients). Bone marrow involvement was not correlated with massive cutaneous mast cell infiltration, clinically or histologically, or with the incidence of clinical symptoms and associated hematologic disorders. None of the patients had experienced progression of clinical symptoms, skin or organ involvement, or development of hematologic malignant neoplasms since UP was first diagnosed (10 years on average). Urticaria pigmentosa was found associated with mast cell infiltration of the bone marrow in 18 patients (60%). However, bone marrow involvement does not seem to predict adverse clinical course.

Adult↗
PubMed1989

Hematopathology of the bone marrow in pediatric cutaneous mastocytosis. A study of 17 patients.

Sixteen bone marrow aspirates and 15 trephine core biopsies from 17 children with cutaneous mastocytosis, of which 15 exhibited urticaria pigmentosa and 2 exhibited diffuse cutaneous mastocytosis, were evaluated for the presence of bone marrow-associated pathologic conditions. Eight bone marrow aspirates from 8 children and 23 trephine core bone marrow biopsies from 16 children who had had evaluation for hematologic abnormalities not associated with cutaneous mastocytosis served as a control population. Eosinophilia was a prominent finding in bone marrows of 9 of 17 patients who had cutaneous mastocytosis. Increased mast cell numbers in bone marrow aspirates were observed in 5 children with cutaneous mastocytosis (5 of 16) and in 2 of the control children (2 of 8). Examination of the trephine core bone marrow biopsies obtained from patients with cutaneous mastocytosis demonstrated focal perivascular and paratrabecular aggregates consisting of mast cells, eosinophils, and early myeloid cells in 10 of 15 individuals. Similar lesions were observed in trephine core bone marrow biopsies of 3 of 16 control patients. The focal mast cell lesions characteristic of adult systemic mastocytosis were not observed. The authors conclude that cutaneous mastocytosis in the pediatric age group is rarely associated with definitive bone marrow findings suggestive of systemic mast cell disease and that this observation is consistent with previous reports that cutaneous mastocytosis in the majority of pediatric cases resolves by adulthood.

Bone Marrow↗
PubMed1998

Hematopathology in dogs experimentally infected with a Swedish granulocytic Ehrlichia species.

Seven, adult, female beagles were inoculated with a Swedish granulocytic Ehrlichia organism closely related to Ehrlichia equi and E. phagocytophila. Blood and bone marrow changes were evaluated throughout the acute phase of infection. All dogs developed moderate to severe thrombocytopenia during the parasitemic period. The mean platelet volume and platelet distribution width increased, and large platelets were seen on blood smears when platelet numbers were low. In bone marrow, absolute numbers of megakaryocytes and immature megakaryocytes were increased. These results suggested the thrombocytopenia was caused by increased platelet destruction. The dogs also developed mild, normocytic, normochromic anemia, with simultaneous decreases in serum iron concentration and total iron-binding capacity that resembled the anemia of inflammation. In bone marrow, there was a slight increase in immature erythroid cells and no erythroid hypoplasia; iron stores were normal to increased. Myeloid hyperplasia was seen in all infected dogs, despite neutropenia in peripheral blood. Lymphopenia occurred early in the parasitemic period, but lymphocytes responded strongly and numbers increased above baseline levels by the end of parasitemia. Blast-transformed lymphocytes (5% to 20%) were seen in peripheral blood for a few days. Experimentally-induced canine granulocytic ehrlichiosis caused cytopenias of short duration, coincident with the appearance of ehrlichial inclusions in neutrophils.

Journal Article↗
PubMed1987

Hematopathological features of acute erythremia (morbus Di Guglielmo). A contribution to the classification and differential diagnosis of erythroid neoplasias.

Classification and differential diagnosis of erythroid neoplasias still are a matter of discussion. Eleven cases of primary acute erythremia were diagnosed between 1981 and 1984 at the Institute of Pathology, University of Kiel. Erythremia represented 0.5% of all hematological diagnoses and 1.0% of the myeloproliferative disorders. The male-to-female ratio was 1:1. Incidence peaked in the 7th decade. Evaluation of clinical data, of cytological and histological findings in blood and bone marrow, and of occasional immunophenotyping of blast cells (anti-glycophorin A+) revealed two variants of acute erythremia: a first, blastic one and a second, more differentiated form. Acute erythremia must be strictly distinguished from mixed erythroid/myeloid erythroleukemia and from secondary erythroid neoplasias, especially the erythremic 'blast crisis' of chronic myeloid leukemia or polycythemia vera rubra. Distinguishing the myelodysplastic variant of sideroblastic anemia from anerythremic acute erythremia can be extremely difficult. We discuss the differential diagnosis and classification of erythroid neoplasias based upon reproducible hematological criteria to facilitate the gathering and comparison of epidemiological and clinical data on these rare malignancies.

Acute Disease↗
PubMed1979

Diagnostic applications of an immunoperoxidase method in hematopathology.

The diagnostic usefulness and reliability, in particular in relation to methodologic problems and limitations, of an immunoperoxidase method are discussed, based upon an initial 3-yr experience with more than 400 cases. It has been found necessary to employ certain control preparations in each study case in order to avoid interpretational errors which can derive from variation in distribution of plasma proteins, in preservation of immunoreactivity with different fixatives, and in nonspecific binding of antiserum. The method is suitable for detection of immunoglobulin components only among lymphoid cells corresponding to late stages in the (B-cell) sequence of transformation. One case has been identified in which the results of the method are inconsistent with additional data, that of large cell neoplasm of apparent epithelial nature with a monotypic immunoglobulin staining pattern. Cytoplasmic lysozyme was present in a variety of different disease processes, including adenocarcinoma and granulocytic, monocytic, and histiocytic proliferations.

Diagnosis, Differential↗