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PubMed1999

Idiopathic thrombocytopenic purpura associated with breast cancer: a case report and review of the current literature.

The association of solid tumors with idiopathic thrombocytopenic purpura (ITP) is rare. Before this study, there have been three case reports indicating an association between breast cancer and ITP. We present a 69-year-old man with metastatic breast cancer and progressive thrombocytopenia without any evidence of a leukoerythroblastic picture or etiologies for the thrombocytopenia. Serum platelet antibodies were identified. A bone marrow biopsy showed small foci of metastatic breast cancer, thrombocytopenia, and normal number of megakaryocytes. A subsequent trial of steroids resulted in a marked improvement of the patient's thrombocytopenia. This is the fourth case report indicating an association of breast cancer and ITP.

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PubMed1988

Remission of chronic idiopathic myelofibrosis to busulfan treatment.

Three patients with chronic idiopathic myelofibrosis have responded to busulfan treatment with an excellent hematologic remission and reversal of myelofibrosis and myeloid metaplasia. Four months after busulfan therapy all three patients showed an improvement of hematocrit and hemoglobin and reduction of the number of leukoerythroblasts. Cellular bone marrow was re-established in two patients. A decrease of hepatomegaly and splenomegaly also occurred and was well correlated with the hematologic response. In one patient, when busulfan was discontinued for about 2 years after achieving an excellent remission, hematologic relapse was accompanied by increase of hepatomegaly and splenomegaly. When busulfan treatment was resumed, hematologic response and decrease of hepatomegaly and splenomegaly reoccurred. This observation has demonstrated the beneficial effect of busulfan in chronic idiopathic myelofibrosis; therefore, the role of busulfan in the management of this disease should be further investigated.

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PubMed1987

Disseminated rhabdomyosarcoma of the urinary bladder in an adult.

A rare case of alveolar rhabdomyosarcoma of the urinary bladder, manifested as a systemic disease in a 51-year-old woman, was diagnosed at necropsy. Diffuse lytic bone lesions and extensive bone marrow involvement with a leukoerythroblastic blood picture led to an initial clinical diagnosis of a hematologic malignancy.

Bone Marrow↗

PubMed1979

The multiple hematologic manifestations of neuroblastoma.

The hematologic manifestations of neuroblastoma are numerous and varied. Bone marrow invasion by tumor cells may cause leukoerythroblastic changes or depression of one or more of the cell lines in the peripheral blood; occasionally bone marrow involvement may be so extensive that tumor cells may be released into the peripheral blood and lead to an erroneous diagnosis of leukemia. Anemia in neuroblastoma patients may result not only from bone marrow involvement, but also from bleeding into a tumor mass or from the hemolysis accompanying a consumption coagulopathy. A specific morphologic abnormality, the cogwheel erythrocyte, has been reported in patients with neuroblastoma. Neuroblastoma may also be associated with elevation of the platelet count or a hypercoagulable state. Recognition of these protean hematologic manifestations may facilitate diagnosis in children with atypical presentations of this highly malignant tumor.

Anemia↗

PubMedDate not supplied

Pre-B acute lymphoblastic leukemia in a 3-year-old boy with pre-acute myelogenous leukemia myelodysplastic syndrome: cytogenetic evidence of common early progenitor cell ontogeny.

PURPOSE: Myelodysplastic syndromes in children commonly evolve into acute leukemia, usually acute myelogenous leukemia (AML) and rarely acute lymphoblastic leukemia (ALL). The lineage of the leukemia can be predicted based on characteristic morphologic and cytogenetic findings of the marrow and peripheral blood. PATIENT AND METHODS: A 3-year-old boy had refractory anemia with excess blasts and abnormalities suggestive of pre-AML with highly unusual cytogenetic changes. ALL of pre-B phenotype developed. RESULTS: Leukoerythroblastic anemia, pseudo Pelger-Huet neutrophils, and dysmyelopoietic hyperplasia of the marrow suggested likely early progression to AML. Complex cytogenetic abnormalities (monosomy 17 and 20, ring chromosome 11 with deletion of bands q23, and a derivative dicentric chromosome 12) were present in both the myelodysplastic marrow and the subsequent ALL. CONCLUSION: This case presents cytogenetic evidence of common early progenitor cell ontogeny of both malignancies (refractory anemia with excess blasts and ALL).

Anemia, Refractory, with Excess of Blasts↗

PubMed1987

Excess of blood group B in primary myelofibrosis.

The distribution of ABO and Rhesus (D) blood groups was studied retrospectively in 40 patients with primary myelofibrosis (PMF). Only patients with a leukoerythroblastic peripheral blood, splenomegaly and marrow fibrosis in whom chronic myeloid leukemia and secondary myelofibrosis was absent were included in the study. In 14 patients (35%), PMF was preceded by another myeloproliferative disorder (polycythemia rubra vera, essential thrombocythemia or unclassified myeloproliferative disorder), while 26 patients (65%) represented agnogenic myeloid metaplasia (AMM). Comparison with Hospital and Irish blood group distribution showed a significant increase in blood group B (p less than 0.01) in PMF. This increase remained statistically significant for both the AMM and the non-AMM subgroup of PMF when each subgroup was considered separately. This finding supports previous suggestions that the various myeloproliferative disorders which proceed to myelofibrosis are a closely related group rather than a heterogeneous collection of diseases.

Humans↗

PubMed1989

Primary (essential) thrombocythemia versus initial (hyperplastic) stages of agnogenic myeloid metaplasia with thrombocytosis--a critical evaluation of clinical and histomorphological data.

In 40 patients (17 male, 23 female, median age 57 years) with the presumptive diagnosis of primary (essential) thrombocythemia (PTH) according to the diagnostic requirements of the Polycythemia-Vera-Study-Group (PVSG) a follow-up study and a histological evaluation of initial trephine biopsies of the bone marrow were performed. Thorough review of the hematological data during the lengthy course of disease (observation time ranging from 1.5-10.5 years) and the histomorphology of the bone marrow implied a discrimination into two groups of patients. Group I patients (n = 26; 10 male, 16 female) were compatible with PTH according to our follow-up studies. Group II patients consisted of 14 cases (7 male, 7 female) which suggested retrospectively early hyperplastic stages of agnogenic myeloid metaplasia (AMM) with concomitant thrombocytosis. In PTH (group I patients) there was a sustained elevation of the platelet count lasting for several years accompanied by stable other blood values. Early AMM (group II patients) was characterized by an insidious decline of the initially elevated thrombocyte count, starting in a few patients already 4-6 months after admission. In AMM there was further an increase in hepatosplenomegaly observable together with the level of LDH and the score of the leukocyte alkaline phosphatase, and finally an evolution of a leukoerythroblastic blood picture could be noticed. Initial histopathology of the bone marrow revealed a profound proliferation of a not severely dysplastic megakaryopoiesis in group I patients (PTH) and a normal content of reticulin fibers. In early thrombocythemic AMM (group II patients) conspicuous abnormalities of megakaryocytes were accompanied by a slight to moderate increase in argyrophilic fibers and a left-shifted neutrophilic granulocyto- as well as erythropoiesis. These differences of certain histomorphological features could be substantiated by morphometric analysis. Our findings suggest that even the rigid requirements for the diagnosis of PTH as proposed by the PVSG may not be sufficiently restrictive to exclude patients with early hyperplastic stages of thrombocythemic AMM.

Biopsy, Needle↗

PubMed2006

Gastric carcinoma presenting with extensive bone metastases and marrow infiltration causing extradural spinal haemorrhage.

Gastric carcinoma is the third most common gastrointestinal (GI) malignancy after colon and pancreatic carcinoma. A Japanese study showed that the incidence of bone metastases of gastric cancer was 13.4% among autopsies. It is very rare for the primary presentation of a gastric malignancy to be with bone metastases. This case report is of a 46-year-old female patient, who presented with a thoracic vertebral wedge fracture and was subsequently found to have widespread vertebral metastatic deposits with marrow infiltration. The infiltration and suppression of marrow function was complicated by an acute bleed into the extradural space causing spinal cord compression. This case demonstrates two important features. First, that gastric cancer, although far less common than breast, kidney, thyroid, prostate and bronchial cancer, is a cause of metastases to bone. Second, it highlights the complications of bone metastases, marrow suppression, leukoerythroblastic anaemia, spinal canal haematoma and cord compression. The case is illustrated by axial and sagittal MRI slices.

Back Pain↗

PubMed2000

Hepatosplenic gamma-delta T-cell lymphoma as a late-onset posttransplant lymphoproliferative disorder in renal transplant recipients.

We report 2 cases of renal transplant recipients in whom hepatosplenic gamma-delta T-cell lymphoma (gamma-delta HSTCL) developed 5 and 10 years after transplantation. Both patients had marked hepatosplenomegaly, B symptoms (weight loss, fever, and night sweats), and abnormal peripheral blood findings, including anemia in both, thrombocytopenia and leukoerythroblastic changes in 1, and leukocytosis in the other. Markedly atypical lymphoid infiltrate of intermediate to large cells was observed in the spleen, liver, and bone marrow. The malignant cells showed typical immunophenotype of gamma-delta T cells (CD2+, CD3+, CD4-, CD8-, CD7+, gamma-delta T-cell receptor-positive, and alpha-beta T-cell receptor-negative) with clonal T-cell receptor gene rearrangement and were of the V-delta-1 subset. In addition, the cells contained a cytolytic granule-associated protein, TIA-1, and Fas ligand, indicating cytotoxic T-cell differentiation. The malignant T cells in both cases were of host tissue origin. Both cases were negative for Epstein-Barr virus genome using Southern blot analysis. The patients did not respond to reduction of immunosuppression. Despite initial response to chemotherapy, both patients died within 6 months of diagnosis. Our findings indicate that gamma-delta HSTCL can occur as a late complication in transplant recipients.

Adult↗

PubMed1998

Multiple diffuse fibrosarcoma of bone associated with extramedullary hematopoiesis.

We report a case of multiple diffuse fibrosarcoma of bone. The patient, a 38-year-old man, was referred to our hospital with knee pain, anemia and thrombocytopenia. No solid mass was seen on radiographic examination of the kneejoint, but magnetic resonance imaging showed hypointensity of the distal femur. Femoral biopsy revealed proliferation of long spindle-shaped fibrosarcoma cells, while a bone marrow biopsy of iliac bone (which appeared normal on radiographic examinations) showed replacement of hematopoietic cells by fibroblast-like spindle cells. A diagnosis of multiple diffuse fibrosarcoma of bone was therefore made. Autopsy revealed tumor invasion into multiple bones and several visceral organs and extramedullary hematopoiesis in the liver, spleen and lymph nodes. As this patient had leukoerythroblastic anemia with poikilocytosis, splenomegaly exhibiting extramedullary hematopoiesis, and apparent fibrotic change in his bone marrow, we suggest that this extremely rare disease should be considered in the differential diagnosis of myelofibrosis.

Adult↗

PubMed2004

Myelofibrosis with myeloid metaplasia: new developments in pathogenesis and treatment.

Myeloid metaplasia with myelofibrosis (MMM) is a chronic myeloproliferative disorder (CMPD) characterized by progressive anemia, massive splenomegaly, both hepatosplenic and non-hepatosplenic extramedullary hematopoiesis (EMH), a leukoerythroblastic blood smear, circulating progenitor cells, and marked bone marrow stromal reaction including collagen fibrosis, osteosclerosis and angiogenesis. The overall median survival is 5 years although it might range from 2 to 15 years depending on the presence or absence of clinically defined prognostic factors. Death is often due to leukemic transformation, portal hypertension or infection. In addition to shortened survival, quality of life is often affected by frequent red blood cell transfusions, profound constitutional symptoms, and cachexia. Drug therapy and autologous hematopoietic stem cell transplantation (HSCT) are of only palliative value and have not been shown to improve survival. The role of allogeneic HSCT, both myeloablative and non-myeloablative, is actively being investigated. Both splenectomy and radiation therapy have defined therapeutic roles to control EMH-associated symptoms. Analysis of the molecular biology of the disease is underway with the aid of animal models leading to the identification of novel therapeutic targets. Among the novel agents tested, thalidomide seems the most promising although newer agents are on the horizon.

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PubMed1988

Effect of chemotherapy on tear drop poikilocytes and other peripheral blood findings in myelofibrosis.

A leukoerythroblastic blood picture and tear drop shaped red cells are two characteristic features of myelofibrosis (MF). Following our earlier observation of an increase in the hemoglobin level with chemotherapy, we have now reviewed the pre- and post-treatment peripheral blood smears from 14 patients with MF to assess the effect of treatment on the above mentioned peripheral blood features. Our results suggest that these features are reversible with effective chemotherapy.

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PubMedDate not supplied

Elevated tumor necrosis factor-alpha in association with severe anemia in human immunodeficiency virus infection and Mycobacterium avium intracellulare infection.

Mycobacterium avium intracellulare (MAI) infection is a serious opportunistic infection that occurs in children with human immunodeficiency virus (HIV) infection. In MAI the hematologic system is profoundly affected. In the present study the hematologic manifestations of MAI in 37 HIV-infected infants and children were reviewed. Anemia was the predominant feature in all patients, with severe anemia (hemoglobin < 6 g/dL) occurring in 7 of 34 (21%) patients. This was followed by leukopenia (79%), monocytosis (82%), thrombocytopenia (59%), leukoerythroblastic reaction (68%), and neutropenia (41%). Serum tumor necrosis factor (TNF)-alpha was markedly elevated in all patients with MAI with an X +/- SE of 702 +/- 182 pg/mL. There was an association between elevated TNF-alpha and anemia in these patients.

AIDS-Related Opportunistic Infections↗

PubMed2000

Bone marrow necrosis in adult acute leukemia and non-Hodgkin's lymphoma.

Bone marrow necrosis is a rare finding in adult patients diagnosed with acute leukemia or non-Hodgkin's lymphoma. Previous reports have suggested that it is associated with a poor prognosis. It remains unclear however, whether improvements in patient care during the last decade have altered patient outcome. In a retrospective review of 581 bone marrow biopsies performed ante mortum on adult patients with acute leukemia or non-Hodgkin's lymphoma, we identified 10 cases of bone marrow necrosis (5 acute myeloid leukemia, 5 non-Hodgkin's lymphoma). Severe bone pain, elevated serum lactate dehydrogenase levels and leukoerythroblastic peripheral blood smears were common presenting features. Despite treating 8 of the 10 patients with curative intent, only 2 patients remain alive and disease-free. This study confirms that bone marrow necrosis in adults with acute leukemia and non-Hodgkin's lymphoma is a rare ante mortum finding and confers a poor prognosis. Whether these patients would benefit from more intensive therapy such as hematopoietic stem cell transplantation remains to be clarified.

Acute Disease↗

PubMed1995

Fatal bone marrow necrosis following fludarabine administration in a patient with indolent lymphoma.

We report the first known case of fulminant bone marrow necrosis (BMN) occurring after infusion of fludarabine monophosphate in a patient with recurrent low-grade non-Hodgkin's lymphoma (NHL). Extensive BMN is characterized by the development of fever, bony pain, a leukoerythroblastic peripheral blood film, variable degrees of pancytopenia and elevations in lactate dehydrogenase and alkaline phosphatase. The diagnosis of BMN is rarely entertained ante-mortem. Although the precise role chemotherapy may have played in triggering fatal BMN remains speculative, we alert clinicians to be aware of this entity as more patients with indolent lymphomas and leukemias are treated with this and other potent nucleoside analogs.

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PubMed1976

Premature chromosome condensation in human leukemia.

Premature chromosome condensation (PCC) has previously been observed in tissue culture and is believed to arise from asynchronous mitotic activity in multinucleated cells in which the affected nucleus is in interphase and at least one nucleus is in metaphase. Such cells have been noted following fusion induced by virus infection, spontaneously, and after treatment with cytochalasin B. The phenomenon has also been observed in malignant pleural effusions, but has not previously been described as a feature of hematologic disease. In this study, we report the observations of PCC in seven patients. Six of these patients had either acute myeloblastic leukemia or acute myelomonoblastic leukemia in association with the features of erythroleukemia, i.e., leukoerythroblastic reaction in the blood, and erythroid multinuclearity, "megaloblastoid" changes, and PAS-positive staining of erythroid precursor cells in the bone marrow. In all patients, erythroid multinuclearity has been noted. However, not all patients with erythroleukemia exhibit PCC. In this series, three additional patients have had similar bone marrow morphologic changes without PCC. The finding of PCC in erythroleukemia may have important implications as to etiology of this disorder.

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PubMed2000

Bone marrow necrosis.

BACKGROUND: In the medical community, little is known regarding bone marrow necrosis (BMN) as a clinicopathologic entity, although to the authors' knowledge it was described for the first time more than 50 years ago. To identify the rate of prevalence, the symptoms and signs, the underlying disease associations, and the usefulness of diagnostic procedures, an extensive literature search was made. METHODS: Only cases identified as extensive necrosis and diagnosed during life were selected. Two hundred forty cases met these criteria. RESULTS: Bone pain (75%) and fever (68.5%) were the most important symptoms, whereas anemia (91%) and thrombocytopenia (78%), associated with a leukoerythroblastic picture (51%), were the most frequent hematologic abnormalities. Nearly 50% of patients showed elevated lactate dehydrogenase and alkaline phosphatase levels. In 90% of the patients an underlying malignancy was identified. CONCLUSIONS: Bone marrow necrosis is caused by hypoxemia after failure of the microcirculation. Given the high rate of malignancy as an underlying disease association, an extensive search for neoplastic disease is justified whenever BMN is diagnosed. Pancytopenia and embolic processes are major complications that should be managed with supportive measures until effective treatment of the underlying disease has been administered. When necrosis resolves, repopulation of the bone marrow cavity with normal hematopoiesis is observed.

Anemia↗

PubMed2003

Primary bone marrow B-cell lymphoma: report of four cases.

Bone marrow involvement is infrequent at presentation in cases of diffuse large B-cell lymphoma. We report four adult patients with diffuse large B-cell lymphoma in whom bone marrow involvement with hematologic manifestations was the predominant clinical feature at presentation. Three patients presented with a leukoerythroblastic blood picture and one with pancytopenia. In each case, the unusual hematologic manifestations, with bone marrow replacement and the presence of immature forms in the peripheral blood, led to consideration of alternative hematologic diagnoses, including acute granulocytic leukemia in three cases and a myelodysplastic syndrome in one. The correct diagnoses were established by immunohistochemistry on formalin-fixed, paraffin-embedded bone marrow for two cases and by flow cytometry on aspirated bone marrow or peripheral blood lymphocytes for the other two. Diffuse large B-cell lymphoma should be considered in the differential diagnosis of unusual hematologic presentations, particularly in the elderly.

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