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.     

Marked bone marrow necrosis preceding acute myeloblastic leukemia in childhood

A 3-year-old boy was transferred to our hospital because of fever, abdominal pain and severe systemic bone pain on October 16, 1989. Hematological examination showed hemoglobin 8.7 g/dl, white blood cell count 5300/microliters with 9% neutrophils and platelet count 5.5 x 10(4)/microliters. Bone marrow aspiration and biopsy revealed markedly necrotic cells. Blood chemistry showed transient elevation of CRP, serum LDH, FDP, FDP-Ddimer and fibrinogen. Tc99m pyrophosphate bone scanning showed multiple uptake spots in various bone. Although the sign of fever, abdominal pain and bone pain disappeared spontaneously after three weeks, anemia persisted. About two months later from bone marrow necrosis, abnormal cells appeared in the bone marrow. A diagnosis of AML (M3) was made and a combination chemotherapy started. This case is remarkable for elevation of acute phase protein in association with bone marrow necrosis.     

Plasma Proteins Case Report: Massive Bone Marrow Necrosis with Polyclonal Hypergammaglobulinemia and Blue Toe Syndrome

Massive bone marrow necrosis was rare, and most of these cases were accompanied with malignant disease. We report a case that was thought to be idiopathic massive bone marrow necrosis. It was a 58 y.o. male who was admitted because of blue toe syndrome and hypergammaglobulinemia. We tried to detect malignant diseases with computed tomography and gallium scintigraphy, and infectious diseases with bacterial culture and viral antibodies, but all of them were negative. Pancytopenia and bone marrow necrosis was not improved, and he had died after 5-month hospitalization. Autopsy revealed massive bone marrow necrosis and bone marrow fibrosis after necrosis, but malignant or infectious diseases were not detected. It may be diagnosed as idiopathic massive bone marrow necrosis.     

Minor bcr/abl positive acute lymphoblastic leukemia preceded by knee joint pain due to bone marrow necrosis

A 16-year-old male was referred to our hospital in April 2003 due to severe knee joint pain from five months previously. Lymphoblasts were identified in his peripheral blood, resulting in a diagnosis of acute lymphoblastic leukemia (ALL). Bone marrow examination revealed massive necrosis with clusters of lymphoblasts and the bcr/abl fusion gene. Magnetic resonance imaging (MRI) of the knee joint showed low signal intensity on T1-weighted images, and peripheral rim enhancement on Gd-DTPA enhanced fat suppression images, which was compatible with bone marrow necrosis. After the patient achieved complete remission (CR), the knee joint pain has disappeared. He was treated with an allogeneic bone marrow transplantation (BMT) from an HLA-identical unrelated donor and has been in CR for 26 months after the diagnosis of ALL. In the knee joint, the replacement of fatty marrow after BMT has been confirmed with MRI. Hematological malignancies including ALL should be considered in the cases of bone marrow necrosis and adequate treatment may improve necrosis.     

Acute unclassified leukemia with bone marrow necrosis

Massive bone marrow necrosis was seen in a 42-year-old male with acute leukemia. In December, 1988, on admission, laboratory data revealed pancytopenia and a high level of serum LDH and ALKP. Bone marrow aspiration resulted in dry-tap and showed bone marrow necrosis in the bone marrow biopsy specimen. A bone marrow scintigraphy with 111In faintly visualized the bone marrow but visualized area was expanded in the extremities compared with normal subjects. The second bone marrow biopsy showed proliferation of blasts. In the middle of March, blasts began to appear in peripheral blood. The blasts were cytochemically negative for POX, Es, PAS, AcP, TdT and had surface markers CD3-, CD19-, CD33-, CD13-, LCA-, HLA-DR-. Even by investigation on rearrangement of the immunoglobulin heavy chain region, an origin of the blasts could not be determined. In April, the number of blasts in peripheral blood increased and hepatosplenomegaly developed rapidly. Therefore, he was put on the chemotherapy with vincristine and prednisolone, but he died of cerebral hemorrhage. The autopsy revealed widespread bone marrow necrosis. It has rarely been reported that massive bone marrow necrosis is found prior to the occurrence of acute unclassified leukemia.     

Pancytopenia due to bone marrow necrosis in acute myelogenous leukemia: Role of reactive CD8 cells

Bone marrow necrosis is a rare clinical condition often associated with hematological malignancy. The mechanism by which malignant disease causes marrow necrosis is unknown. We present a case of a patient with newly diagnosed pancytopenia with bone marrow biopsy evidence of extensive marrow necrosis. Upon further work-up utilizing Tc bone scan directed bone marrow biopsy, a massive CD8+ T cell marrow infiltrate was discovered engulfing AML-M2 blasts. The role of Tc bone scans in the work-up of bone marrow necrosis as well as the potential mechanism of AML-M2 induced marrow necrosis in the setting of reactive CD8+ T cell infiltration is discussed. Am. J. Hematol. 59:74– 78, 1998. © 1998 Wiley-Liss, Inc.     

Recurrence of Acute Lymphoblastic Leukemia with Bone Marrow Necrosis: A Case Report and Review of the Literature on the MRI Features of Bone Marrow Necrosis

Bone marrow necrosis (BMN) is a rare but important complication of hematological malignancies. We report the case of a 52-year-old male patient with a recurrence of acute lymphoblastic leukemia (ALL) accompanied by BMN. After re-induction therapy, bone marrow aspiration (BMA) and biopsy from the iliac bone showed necrotic cells and eosinophilic debris, respectively. Magnetic resonance imaging (MRI) showed heterogeneous signals in the bilateral iliac bone, possibly reflecting various stages of BMN. BMA from the sternum eventually revealed the recurrence of ALL after a few weeks. Comprehensive assessments, including MRI and repeated bone marrow tests, are required when evaluating the underlying hematological malignancies of patients with BMN.     

Extensive bone marrow necrosis and symptomatic hypercalcemia in B cell blastic transformation of chronic myeloid leukemia: report of a case and review of the literature

Extensive bone marrow necrosis and symptomatic hypercalcemia have been described independently as rare complications of chronic myeloid leukemia. Here we report a 66-year-old man who developed B cell blastic transformation 10 years after diagnosis of CML in the chronic phase. Extensive bone marrow necrosis and symptomatic hypercalcemia concurrently developed after transformation, with development of disseminated intravascular coagulation and multifocal osteolysis. Most necrotic cells were readily identifiable as blasts. Mediators related to hypercalcemia, including prostaglandin E2, transforming growth factor-alpha and transforming growth factor-beta, were significantly elevated in the serum. As far as we know, this is the first case report of chronic myeloid leukemia concurrently developing bone marrow necrosis and hypercalcemia; this association was not reported in other types of leukemia or bone marrow malignancies.     

Diagnosis of bone marrow necrosis

Two cases of bone marrow necrosis (BMN) were diagnosed during life. Both patients developed BMN as a terminal event in the evolution of untreated malignant lymphoma. No earlier cases of BMN in untreated malignant lymphoma are reported in the literature. In one patient necrotic and normal bone marrow were simultaneously obtained from two different aspiration sites, showing the focal nature of the process. BMN itself being reversible, the diagnosis in vivo is important. A better knowledge of the significance of a yellow brown viscous fluid obtained by bone marrow aspiration and the exact interpretation of necrotic bone marrow films are essential to recognition of BMN.     

Relationship between magnetic resonance imaging and histologic findings by bone biopsy in nontraumatic osteonecrosis of the femoral head.

To attest the validity of magnetic resonance imaging (MRI) to evaluate the pathophysiology in nontraumatic osteonecrosis (ON) of the femoral head, we attempted to correlate the different MRI patterns with the histology in cases of early stages. We used not only the T1 and T2 pulse sequences, but also the T1 sequence after gadolinium-DTPA to demonstrate the presence of vascularization. Studying 24 core biopsies from 16 hips (9 patients), we explored the MRI presentations that corresponded to the main histologic findings of the different trabecular bone and bone marrow conditions. Histologic findings including trabecular bone necrosis and bone marrow necrosis represented by amorphous eosinophilic debris presented a low T1 signal intensity without enhancement after intravenous gadolinium injection and a low T2 signal intensity. Trabecular bone necrosis associated with mummified fat cells presented a normal T1 and T2 signal intensity. Trabecular bone necrosis with fibrosis filling the intertrabecular spaces had a low T1 signal intensity that was enhanced by gadolinium and had an intermediate T2 signal intensity. Bands of fibrosis without trabecular bone as seen in fracture zones showed a low T1 signal intensity that was enhanced by gadolinium with a high T2 signal intensity. Thickened trabecular bone with fibrosis as found in creeping substitution areas had also a low T1 signal enhanced by gadolinium, but the T2 signal intensity was low. Farther from the necrotic area, despite normal trabecular bone, we found some patchy necrosis of the bone marrow without any modification of the normal T1 and T2 MRI patterns.(ABSTRACT TRUNCATED AT 250 WORDS)     

Appearance of Bone Marrow Smears With Necrotic Tumor Cells

Bone marrow smears of necrotic tumorcells stained with Romanowsky dyes frequently have a definite reddish colorthat contrasts so strikingly with the bluecolor of normal marrow that necrosismay be suspected from gross examination. The bone marrow cells appear"smudged" and are difficult to identifyon microscopic examination. Commonly,only a small amount of material is obtainable by ordinary needle aspiration ofbone marrow containing necrotic tumor,and all of it is used to make smears. Itis therefore important to recognize thatbone marrow smears with a reddishgross appearance and in which the cellsappear distorted and are difficult toidentify may represent necrotic tumorand not an artifact produced by poortechniques.

Submitted on March 5, 1971 Accepted on March 22, 1971     

Bone marrow necrosis in two patients with acute promyelocytic leukemia during treatment with all-trans retinoic acid

All-trans retinoic acid has been used for the treatment of acute promyelocytic leukemia (APL) with encouraging results. However, it has recently been associated with a number of potentially serious complications including the retinoic acid syndrome. We describe two patients with APL who were begun on all-trans retinoic acid therapy (45 mg/m²), but who developed leukocytosis which was treated with hydroxyurea. Both patients demonstrated clinical and laboratory findings of disseminated intravascular coagulation, massive cell lysis manifested by marked increases in serum lactic dehydrogenase, and rapid clinical deterioration. Both patients developed bone marrow necrosis within viable, non-infarcted bone trabeculae. We postulate that the development of bone marrow necrosis in these two patients was not a chance occurrence. Rather, the specific combination of cytotoxic and differentiating agents used in these patients (hydroxyurea with all-trans retinoic acid) caused massive cell lysis and death. The absence of bone marrow necrosis in the setting of induction therapy for APL both with and without all-trans retinoic acid therapy suggests that the addition of hydroxyurea was critical to the development of marrow necrosis. We, therefore, recommend caution in the use of hydroxyurea and all-trans retinoic acid in the treatment of APL. © 1994 Wiley-Liss, Inc.     

Clinicohaematological profile of infections in bone marrow - single centre experience in North Himalayan region of India

The bone marrow examination in cases of infections may be non-specific but certain reactive changes may raise high index of suspicion of infections. The present study from a tertiary centre in the North Himalayan region of India describes the clinicohaematological profile and the changes associated with infections in the marrow. The study included all the cases of infections in which bone marrow examination was done during the period between January 2006 and July 2010. Leishmaniasis was the most common infection observed and most of the patients presented with fever along with anaemia and pancytopenia. Bone marrow examination showed predominantly transient myelodysplasia, plasmacytosis, and hemophagocytosis along with associated fibrosis and necrosis. Another important feature observed was accumulation of mature plasma cells around capillaries along with increased iron stores in the marrow. Thus, these features are important indicators of infections and should lead to their vigilant search in the patient.     

以胸腔积液为首发症状的多发性骨髓瘤1例并文献复习

目的 提高对多发性骨髓瘤(MM)诊断的认识.方法 报道1例以胸腔积液就诊的MM病例,并对相关文献进行复习.结果 45岁女性,胸闷、憋气3个月.近1个月有少尿及头痛、头晕症状.胸部CT示右侧液气胸,左侧大量胸腔积液,胸壁见扁丘状软组织影突出.胸腔镜下见胸腔内大量淡黄色液体,脏层胸膜和膈胸膜光滑,壁层胸膜大量大小不一的结节,质硬,活检不易出血的.病理示浆细胞瘤.胸骨穿刺骨髓象检查示大量的浆细胞瘤细胞骨髓浸润.结论 MM患者以髓外病变就诊时,应结合临床表现考虑到MM的可能,及时行骨髓检查明确诊断.并发髓外病变时预后不良.     

Bone Marrow Involvement in Burkitt''s Tumour

The bone marrow aspirates from 100 cases of Burkitt's tumour have been analysed. Eight of these showed diffuse massive infiltration with Burkitt tumour cells and eight showed very scanty tumour cells. A leuco-erythroblastic blood picture with occasional or no tumour cells was commonly found in those cases with diffuse massive bone marrow infiltration. This type of bone marrow involvement carries a poor prognosis, the mean survival time of the eight cases in this series being 33 days. The percentage of lymphocytes in the marrow smears of 20 children with Burkitt's tumour, without tumour cells in their bone marrow, was found to be less than that in the bone marrow smears from 20 control children. This may reflect an impaired immune mechanism in children with Burkitt's tumour.     

Extensive bone marrow necrosis associated with carcinomatosis 7 years after operation for gastric cancer

A case of extensive bone marrow necrosis due to cancer metastasis is reported. A 55-year-old female, who had a history of subtotal gastrectomy for signet ring cell carcinoma of the stomach 7 years ago, was admitted to our hospital with a complaint of lumbago on October 25, 1987. Red blood cell count was 92 X 10(4)/microliters, hemoglobin 2.7 g/dl, hematocrit 8.0%, platelet 6.4 X 10(4)/microliters, and white blood cell count 13,400/microliters with leukoerythroblastosis. Bone marrow aspiration of the sternum, left iliac crest, and bilateral posterior superior iliac supine showed extensive bone marrow necrosis. Serum ALP was increased to 7410IU/l, dominated isozyme of bone type. Hemostatic findings suggested a complication of consumption coagulopathy. Skull, vertebrae, iliac and pelvic bone X-ray showed multiple osteolytic lesions, and irregular isotope uptake was recognized on the bone scintigraphy using 99mTc. Sixth bone marrow examination at the right iliac crest revealed signet ring cell carcinoma metastasis. In spite of detailed examinations, there was no evidence of primary carcinoma, including the remnant of stomach. We speculated that the signet ring cells were originated from the respected gastric cancer. The patient has received anti-cancer chemotherapy with UFT and OK432, and is still alive 9 months after diagnosis.     

EB virus-associated peripheral T cell lymphoma presenting with hemophagocytic syndrome and hepatic cell necrosis

A 72-year-old woman was admitted with left cervical lymphadenopathy, high fever, pancytopenia and liver dysfunction. Bone marrow aspiration showed infiltration of large atypical lymphoid cells and hemophagocytic histiocytes, thus suggesting a diagnosis of lymphoma associated hemophagocytic syndrome (LAHS). An abdominal CT scan revealed multiple low-density areas in the liver, and the patient's liver function rapidly deteriorated. Histologically, the cervical biopsy showed lymphoma cell infiltration with prominent necrosis and karyorrhectic debris. The lymphoma cells expressed CD3+, CD4-, CD8+, CD20-, CD56+/-, TIA-1+, granzyme B+, and EBER was positive using in situ hybridization. DNA analysis of the TCR beta and gamma chain gene with the Southern blot showed rearranged bands. These findings were compatible with those of EB-virus associated peripheral T-cell lymphoma. After chemotherapy with the THP-COP regimen, the patient's liver dysfunction improved rapidly, but she died from bacterial peritonitis due to perforation of a recurrent duodenal ulcer. Post-mortem examination of the liver showed multiple irregular massive necroses of the hepatocytes, where no lymphoma cell infiltration was present. Hemophagocytic histiocytosis was remarkable in the bone marrow, spleen, lymph nodes, and liver. Marked elevation of serum levels of cytokines such as TNF-alpha or IFN-gamma suggests that these cytokines played an important role in the pathogenesis of the hepatic cell necrosis.     

Osteomyelosclerosis with thalassemia trait: report of a rare association, study of platelet function tests and review of literature

Idiopathic myelofibrosis is a chronic myeloproliferative disorder characterized by excessive connective tissue deposition in the bone marrow. It presents with leucoerythroblastic anemia and massive splenomegaly. It is termed osteomyelosclerosis in the presence of primitive bone formation in the bone marrow and radiological presence of osteosclerosis. A 40-year-old male, known case of thalassemia trait presented with fatigue and lump in the abdomen for two months. Physical examination showed splenomegaly 8.5 cm below costal margin. X-ray examination revealed multiple osteosclerotic lesions involving the pelvis and long bones. Hemogram showed: hemoglobin 7.8 gm/dl, TLC 47,500/mm(3); DLC was polymorphs 49%, lymphocytes 7%, eosinophils 4%, basophils 4%, blasts 5%, promyelocytes 2%, myelocytes 14%, metamyelocytes 10%. Platelet count was 60,000/mm(3). Peripheral blood film showed leucoerythroblastic blood picture with features of dysmyelopoiesis. Bone marrow aspiration was diluted with peripheral blood. Bone marrow biopsy showed replacement of marrow by grade III reticulin fibrosis. Bony trabaculae were wide and thick. Platelet function studies were abnormal. The clinical, radiological and hematological features suggested a diagnosis of osteomyelosclerosis. We present this case because no similar association of osteomyelosclerosis with thalassemia trait has been described in English literature to date. This is the first study from India, which describes platelet function tests in a patient with osteomyelosclerosis.     

How I investigate bone marrow necrosis

Hematopathologists encounter bone marrow biopsy specimens with marrow necrosis relatively infrequently; when necrosis is seen, determining the clinical significance can be challenging. While bone marrow necrosis is not uncommon in site‐directed biopsy specimens or autopsy material, substantial necrosis is much less common in nondirected bone marrow biopsy specimens. Retrospective review showed the prevalence of bone marrow necrosis to vary between 0.3% and 2% antemortem, depending on the patient population. Numerous causes of bone marrow necrosis have been identified, including malignancy, radiation/chemotherapy, medication, infection, autoimmune disease, disseminated intravascular coagulation, antiphospholipid syndrome and other thrombotic disorders, granulocyte‐colony stimulating factor (G‐CSF) exposure, and hemoglobinopathies. Clinical findings associated with bone marrow necrosis include bone pain and fever, cytopenias, elevated LDH and ferritin, and leukoerythroblastosis. Rarely, such as in fat embolization syndrome (FES), bone marrow necrosis can be associated with thrombotic microangiopathy, neurologic dysfunction, and multiorgan failure. A thorough review of the patient's clinical record (including medical history, clinical presentation, and other laboratory findings), a thorough morphologic review of the bone marrow with appropriate ancillary stains, and an appreciation of the causes of bone marrow necrosis in different patient populations are required to determine the underlying cause of bone marrow necrosis. The purpose of this review is to present a strategy for evaluation of bone marrow necrosis found in an antemortem biopsy specimen.