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PubMed1978

Variables predictive of bone marrow metastasis.

Metastasis to bone marrow, though frequently occult, is an important clinical finding. Variables which correlate with carcinoma metastatic to bone marrow were studied retrospectively in 103 patients with malignancy whose bone marrow biopsies demonstrated metastatic disease. Sixty-six patients with metastatic cancer whose bone marrow biopsies were negative, served as controls. Since no single finding was diagnostic of marrow cancer, multiple variables were analyzed by stepwise discriminate analysis program. The four parameters which strongly correlated with marrow involvement were the leukoerythroblastic blood pattern, a serum lactic dehydrogenase over 500 IU/liter, a platelet count under 100,000/microliter and bone pain. Four parameters correlated less well and included a positive bone scan, hematocrit under 30%, uric acid over 10 mg/dl and blood urea nitrogen over 25 mg/dl. These data should help the clinician select those cancer patients with a high probability of marrow involvement.

Blood Cell Count↗

PubMed1983

Red cell aplasia in myelofibrosis with myeloid metaplasia. A distinct functional and clinical entity.

Three patients with myelofibrosis with myeloid metaplasia are described. All three presented with grave anemia and red cell aplasia. Erythroid failure was the functional characteristic of erythropoiesis as resulted from erythrokinetic studies. Bone marrow was hypercellular or normocellular with hyperplasia of granuloblasts and megakaryocytes. Despite absent or mild splenomegaly at diagnosis, massive splenomegaly associated with a leukoerythroblastic blood film developed during the course of the disease. A relative young age (42-47 years), a subacute course of the disease and terminal blast crisis in two of them were the prominent clinical features of the patients. The differentiation from acute or malignant myelofibrosis is discussed. The patients appear to be a distinct subset within myelofibrosis with myeloid metaplasia.

Adult↗

PubMed1984

Primary hemangiosarcoma of the spleen with angioscintigraphic demonstration of metastases.

A case of primary hemangiosarcoma of the spleen in a 48-year-old woman is presented. Twenty-eight months after splenectomy the patient developed a severe anemia of the microangiopathic type, thrombocytopenia, and a leukoerythroblastic peripheral blood picture. In contrast to x-ray and conventional 99mTc-methylene-diphosphonate (MDP) bone scintigraphy, which showed only a few minor focal changes in the spine and ribs, angioscintigraphy with in vitro labeled 99mTc-erythrocytes revealed extensive pathologic accumulations throughout the spine, femurs, and the liver, indicating the presence of extremely vascular metastases. Autopsy 15 months later confirmed the scintigraphic findings. Angiography with 99mTc-labeled erythrocytes seems to be useful for monitoring metastases from hemangiosarcomas.

Anemia↗

PubMed1984

Megakaryoblastic transformation in myeloproliferative disorders.

Megakaryoblastic transformation, with cells showing characteristic morphology and ultrastructural cytochemistry, developed in two patients with agnogenic myeloid metaplasia or myelofibrosis, and in one with chronic granulocytic leukemia. From the onset of the leukemic phase, all three have followed a relatively benign clinical course, surviving for 48, 29, and 24 months, respectively; only hydroxyurea has been necessary to control thrombocytosis. This experience emphasizes that it is possible for a patient to have an improved quality of life with minimum chemotherapy. In contrast, megakaryoblastic leukemia or acute myelofibrosis, where splenomegaly and a leukoerythroblastic blood picture are typically absent, responds poorly to any form of chemotherapy, and survival is short.

Blood Cell Count↗

PubMed1993

Spontaneous remission of infantile acute nonlymphocytic leukemia for 11 years in a child with normal karyotype.

BACKGROUND: Leukemia or a leukemia-like picture in phenotypically normal infants with a normal marrow karyotype who undergo spontaneous remission is extremely unusual. RESULTS: A 6-week-old, phenotypically normal boy first was seen in 1979 with hepatosplenomegaly, a 36 x 10(9)/l leukocyte count, a leukoerythroblastic picture, and increased blasts in the bone marrow aspirate. Because no other known causes of leukemoid reaction could be demonstrated, the picture was consistent at that time with acute nonlymphocytic leukemia (ANLL), French-American-British (FAB) M1; however, because of the age of the child, the low blast count, normal cytogenetics, and questions about this diagnosis, treatment was withheld. Hematologic laboratory values normalized by the time he was 1 year of age. Eleven years later, he presented a similar picture that rapidly progressed to overt leukemia (FAB M1). A normal marrow karyotype was consistent throughout the 11 years of follow-up. Treatment of ANLL was initiated, resulting in marrow remission. This was followed by allogeneic bone marrow transplantation. He had a relapse again and was retreated, achieving a second marrow remission, and had a second allogeneic bone marrow transplantation. However, the patient died of venoocclusive disease of the liver after the second transplant. CONCLUSION: The diagnosis and prognosis of infants with an abnormal hematologic picture similar to ANLL but who are phenotypically and karyotypically normal are not as straightforward as in the older child or adult. Treatment should be withheld in this setting until the leukemic process is overt.

Child↗

PubMed1988

Rhabdomyosarcoma presenting with diffuse bone marrow involvement, hypercalcemia and renal failure.

Rhabdomyosarcoma and other small round-cell neoplasms of infancy and childhood frequently involve the bone marrow. An unusual clinical presentation of diffuse bone marrow involvement as the sole manifestation of the disease represents a difficult diagnostic challenge. We report the case of an 18-year-old boy presenting with lower back pain, sternum tenderness, anemia, thrombocytopenia, leukoerythroblastic blood film, hypercalcemia, and renal failure. No solid tumor was found. A diagnosis of rhabdomyoblastic bone marrow metastatic involvement was initially suggested by the morphological picture, and later confirmed by the ultrastructural findings. Hypercalcemia and renal failure were controlled, initially, with furosemide and calcitonin. The patient was treated with intensive chemotherapy, including vincristine, actinomycin D, cyclophosphamide, and doxorubicin. A remission was achieved, lasting 5 months until relapse.

Adult↗

PubMed1988

Intracranial astrocytoma with diffuse bone marrow metastasis: a case report and review of the literature.

A 41 year old male presented with headache, lethargy, and ataxia and found to have a left temporal lobe mass and a leukoerythroblastic peripheral blood smear. The latter prompted an iliac crest bone marrow biopsy on which a diagnosis of metastatic glioma was made and verified by immunohistologic characterization. The patient was treated with cranial irradiation and simultaneous systemic BCNU (bis-dichloroethylnitrosurea) with complete response. This case with diffuse bone marrow involvement demonstrates that a glioblastoma is capable of extracranial metastases without previous intervention. From a review of reported cases of gliomas of extraneural metastasis, it is concluded that untreated gliomas are capable of vascular spread although less frequently than previously manipulated tumors.

Adult↗

PubMed1991

Myelodysplastic syndromes with bone marrow fibrosis: a myelodysplastic disorder with proliferative features.

We report on 22 patients with myelodysplastic syndrome (MDS), all of whom showed striking marrow fibrosis. Variable blood counts, often with teardrop poikilocytosis and a leukoerythroblastic picture, were present at diagnosis. Visceral enlargement was detected in 17 patients with a distinct splenomegaly in seven cases. All cases demonstrated dysplasia in at least two cell lineages. No specific cytogenetic abnormality seems to characterize this group of patients. Southern blot analysis showed no breakpoint cluster region rearrangement as observed in classical chronic myeloid leukemia. Ferrokinetic studies revealed quantitatively deficient erythropoiesis in all except two cases and an abnormally high fraction of ineffective erythropoiesis in all. Splenic erythropoiesis was present in eight patients. The median survival was 18 months. At the time of this report, 12 patients had died. The causes of death were disease progression (7 patients) and infection (5 patients). One might speculate that the present series of cases represents a transition between MDS and myeloproliferative disease, thereby displaying characteristics of both groups of diseases.

Adult↗

PubMed1993

Idiopathic myelofibrosis--an update with particular reference to clinical aspects and prognosis.

Idiopathic myelofibrosis (IMF) is characterized by excessive accumulation of connective tissue in the bone marrow as part of a clinical syndrome which in its classical form is featured by leukoerythroblastic anemia and huge splenomegaly at the time of diagnosis. An acute variant of the disease exists being featured by pancytopenia, nor or minimal splenomegaly and a rapidly fatal clinical course. This review describes the relationship of IMF to other chronic myeloproliferative disorders and highlights current concepts of the pathogenesis of bone marrow fibrosis, implicating the intramedullary release of various growth factors, including platelet-derived growth factor beta. In a subgroup of patients bone marrow fibrosis may develop consequent to autoimmune bone marrow damage. The clinical and laboratory findings in some of the larger series of patients are presented and the reasons for the highly variable clinical presentation and prognosis are critically discussed. It is proposed that studies on prognosis in IMF are based upon simple prognostic staging systems, which should include the Hb-concentration, platelet count, spleen size and the presence/absence of osteomyelosclerosis on X-ray. Using these parameters the patients are easily categorized into three prognostic groups with highly different survival times.

Female↗

PubMed1999

The role of interferon-alpha in the treatment of idiopathic myelofibrosis.

Idiopathic myelofibrosis (IMF) is a chronic myeloproliferative disorder characterized by fibrosis of the bone marrow, varying degrees of extramedullary hematopoiesis, splenomegaly, anemia, and a leukoerythroblastic peripheral blood smear. Bone marrow fibrosis develops as a secondary phenomenon and is caused by increased intramedullary activity of mitogens such as platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and calmodulin. Because of the variable clinical course of IMF, attempts have been made to define prognostic parameters that can be helpful in detecting patients with a shortened life expectancy. The most important adverse prognostic parameters that have been reported are hemoglobin concentration, age, leukocyte count, number of thrombocytes, and cytogenetic abnormalities. However, no standardized prognostic score for IMF has yet been established. Therapeutic strategies in IMF remain predominantly supportive. The most common are blood transfusions, androgens, and cytoreductive agents such as hydroxyurea. Bone marrow transplantation is increasingly being taken into consideration, but it still has to be regarded as an experimental approach. Interferon-alpha (IFN-alpha) has shown promising results in early hyperproliferative stages of IMF but has no or only very little effect in more advanced stages of the disease. Whether IFN-alpha is able to postpone marrow fibrosis if administered in early disease stages remains to be determined in future clinical trials.

Humans↗

PubMed1976

Bone marrow necrosis.

The clinical findings of bone marrow necrosis in 13 patients undergoing bone marrow examination to investigate a peripheral blood cytopenia or leukoerythroblastic blood smear were reviewed and compared to those in the literature. Excluding sickle cell disease, all cases of bone marrow necrosis diagnosed during life were associated with a neoplastic process involving the marrow. A myeloproliferative disorder was found in five patients, metastatic carcinoma in five patients, a lymphoma in two patients, and both a myeloproliferative disorder and metastatic carcinoma in one patient. Marrow necrosis was found to involve the marrow at multiple sites in a piecemeal fashion with areas of necrotic marrow and structurally intact marrow adjacent to each other. Severe bone pain without roentgenographic abnormality was the major symptom in 85% of the patients. Marrow and fat emboli, hypercalcemia and peripheral blood cytopenias were identified as direct complications of marrow necrosis. The prognosis of patients with marrow necrosis secondary to neoplastic disease was found to be extremely poor with a median survival of less than one month. However, one patient responded to antineoplastic chemotherapy and showed healing of the bone marrow.

Adenocarcinoma↗

PubMed1983

Myelofibrosis of the facial bones.

Idiopathic myelofibrosis is a hematologic myeloproliferative disorder characterized by progressive marrow fibrosis, extramedullary hematopoiesis, and a leukoerythroblastic anemia. Consequently there are frequent secondarily precipitated multiple systems problems. This is the first report of this entity presenting with orofacial findings. The histopathogenesis, clinical presentation, and the therapeutic goals of treatment are reviewed.

Aged↗

PubMed2004

Bone marrow metastasis of angiosarcoma.

We report a rare finding of bone marrow metastasis from an angiosarcoma. The patient was a 36-year-old man who initially presented with a high-grade angiosarcoma of the spleen and was treated with splenectomy and chemotherapy. He developed leukoerythroblastic anemia three years after splenectomy. Bone marrow biopsy revealed extensive infiltrate by angiosarcoma with typical features of spindle tumor cells and anastomosing vascular channels. The immunohistochemistry showed tumor cells positive for the endothelial markers of CD31, CD34, and von Willebrand factor. Angiosarcomas are rare and aggressive tumors. Although metastases occur commonly, bone marrow findings have been rarely documented. We have found in the literature two other cases of bone marrow metastasis of angiosarcoma, and all these patients had a primary tumor of the spleen. It would seem that splenic angiosarcomas have a virtually unique propensity for infiltration in the bone marrow.

Adult↗

PubMed1990

Autoimmune hemolytic anemia in Kawasaki disease: a case report.

A 3-year-old boy presented with the fever, conjunctivitis, rash, and lymphadenopathy diagnostic of Kawasaki disease. Treatment with antibiotics, aspirin, and intravenous immunoglobulin was instituted. The hematocrit decreased from 35 percent on admission to 11 percent by hospital Day 10, and the white cell count had increased from 13.7 to 42 x 10(3) per microL, and the patient had a leukoerythroblastic blood smear. The direct antiglobulin test demonstrated IgG but not complement on the red cell (RBC) surface. An acid eluate reacted (titer of 4) with all panel cells in the antiglobulin phase. Intravenous immunoglobulin from the same lot used for treatment did not contain antibody that reacted with the patient's group O RBCs or a panel of group O RBCs, but did contain IgG anti-A and -B (titer of 4). The patient received a transfusion and was given methylprednisone. The direct antiglobulin test and acid eluate were negative 4 days later. The patient had an uneventful recovery. The distinction between antibody-mediated hemolytic anemia and autoimmune hemolytic anemia is important in the treatment of this disease.

Anemia, Hemolytic, Autoimmune↗

PubMed1987

Human parvovirus infection in pregnancy and hydrops fetalis.

Human parvovirus is the causative agent of erythema infectiosum, a mild epidemic illness. In a recent outbreak in northeast Scotland, six women had serologic evidence of having contracted human parvovirus infection during pregnancy. Two of the women had midtrimester abortions, and both abortuses were grossly hydropic with anemia. They had similar microscopical histopathological features--a pronounced leukoerythroblastic reaction, hepatitis, excessive iron pigment in the liver, and eosinophilic changes in the hematopoietic cell nuclei. Dot hybridization with radiolabeled human parvovirus DNA probes revealed viral DNA in several tissues from both fetuses, indicating that they had been infected by the virus in utero. The remaining four women had uncomplicated pregnancies and delivered apparently healthy babies, none of whom had human parvovirus-specific IgM antibody at delivery. We conclude that this common virus may pose a serious risk to the fetus after maternal infection.

Abortion, Septic↗

PubMed2003

Bone marrow infiltrate by a poorly differentiated neuroendocrine carcinoma.

We report a rare case of bone marrow infiltrate by a neuroendocrine carcinoma. The patient was a 66-year-old man who presented with anemia and thrombocytopenia and with a leukoerythroblastic picture on blood films. A bone marrow biopsy revealed extensive tumor infiltrate with morphological and immunohistochemical features of neuroendocrine origin. There were also multiple nodular lesions in the liver, which showed the same pathology as that in the bone marrow. Since none of the lesions could be identified as the primary tumor, the patient was diagnosed to have a poorly differentiated neuroendocrine carcinoma of unknown primary site.

Aged↗

PubMed2005

Agnogenic myeloid metaplasia with pulmonary hematopoiesis.

Agnogenic myeloid metaplasia (AMM) is characterized by bone marrow fibrosis, splenomegaly and leukoerythroblastic anemia and is frequently accompanied by extramedullary hematopoiesis (EMH). Pulmonary interstitial EMH associated with myelofibrosis has rarely been described in the medical literature and is usually fatal. We report the case of a 77-year-old man with agnogenic myeloid metaplasia (AMM) treated with hydroxyurea, who seven years after diagnosis presented with dyspnea and severe hypoxemia. Radionuclide bone marrow scanning demonstrated increased tracer activity on the bases of both lungs, consistent with non-hepatosplenic EMH. Pulmonary EMH is rare in patients with AMM, but should be considered in patients with hypoxemia and respiratory distress.

Aged↗

PubMed2002

Idiopathic myelofibrosis associated with primary biliary cirrhosis.

A patient with primary biliary cirrhosis (PBC) who developed idiopathic myelofibrosis (IM) is reported. The initial diagnosis of PBC was established by liver biopsy, performed after a 2-month history of constitutional symptoms associated with abnormalities of the serum liver enzymes, with typical serum immunological markers being found. Although a favorable response of PBC to prednisone was observed, one and a half year later the patient developed anemia with anisocytosis and poikilocytosis, tear-drop cells, and leukoerythroblastic picture, and IM was diagnosed by bone marrow biopsy. A few months later, a rapid worsening of the patient's clinical condition was noted, with an increase in the constitutional symptoms and need for frequent packed RBC transfusions, and she finally died from an infectious complication. This case represents a new association of IM with an autoimmune disease, supporting the hypothesis of a possible immune basis of IM in some cases.

Aged↗