Bone Marrow Necrosis Research Articles

Bone marrow necrosis in dogs: 34 cases (1996–2004)

To identify the incidence, potential causes, and clinical and clinicopathologic features of bone marrow necrosis in dogs. Retrospective study. 34 client-owned dogs. Reports of cytologic examinations of bone marrow specimens performed between 1996 and 2004 were reviewed. All reports that indicated the presence of necrosis, stromal disruption, phagocytic macrophages, individual cell necrosis, or myelofibrosis were evaluated further. Of 609 reports of bone marrow evaluations performed during the study period, 34 (5.6%) had evidence of bone marrow necrosis. Nine dogs had no evidence of associated diseases or drug or toxin exposure, and 25 dogs had associated disease conditions or drug exposures. All 9 dogs with idiopathic bone marrow necrosis were anemic (mean Hct, 14%), but only 3 had neutropenia, and 3 had thrombocytopenia. All 9 had myelofibrosis. Of the 25 dogs with associated disease conditions or drug exposures, only 14 (56%) had anemia (mean Hct, 33%). In addition, 14 (56%) had neutropenia and 18 (72%) had thrombocytopenia. Only 10 (40%) had myelofibrosis. Results suggest that bone marrow necrosis may be common in dogs with hematologic disorders. In most dogs, bone marrow necrosis was associated with an underlying disease condition or drug exposure, but idiopathic bone marrow necrosis was also identified. Disease conditions that should increase suspicion of possible bone marrow necrosis include sepsis, lymphosarcoma, and systemic lupus erythematosus; drug exposures that should increase suspicion of possible bone marrow necrosis include chemotherapeutic agents, phenobarbital, carprofen, metronidazole, and mitotane.

MAGNETIC RESONANCE IMAGING FINDINGS IN THE EQUINE DEEP DIGITAL FLEXOR TENDON AND DISTAL SESAMOID BONE IN ADVANCED NAVICULAR DISEASE—AN EX VIVO STUDY

We describe the abnormal magnetic resonance (MR) imaging findings in the deep digital flexor tendon (DDFT) and distal sesamoid bone in horses with radiographic changes compatible with navicular syndrome. Thirteen postmortem specimens were examined using a 1.5-T magnetic field, with spin echo (SE) T1-weighted, turbo SE (TSE) proton density-weighted (with and without fat saturation), and fat saturation TSE T2-weighted sequences. The limbs were then dissected to compare the MR findings with the gross assessment and histologic examination of the DDFT and distal sesamoid bones. Tendonous abnormalities were detected by MR imaging in 12 DDFTs and confirmed at necropsy. Most tendon lesions were located at the level of the distal sesamoid bone and the proximal recess of the podotrochlear bursa. Tendon lesions were classified based on their MR imaging features as core lesions, dorsal lesions, dorsal abrasions, and parasagittal splits. Areas of increased MR signal in the DDFTs were characterized by tendon fiber disturbance and lack of continuity of the collagen fibers, foci of edema, hemorrhages, and formation of lakes containing eosinophilic plasma-like material or amphophilic material of low density. Bone marrow signal alterations in the distal sesamoid bone were seen in all digits. Two main phenomena were responsible for the abnormal signal, respectively, in T1-weighted (decreased signal) and in T2-weighted fat-suppressed images (increased signal): a decrease in the fat marrow content in the trabecular spaces and an increase in the fluid content. Histologic examination revealed foci of bone marrow edema, hemorrhage, necrosis, and fibrosis. Cyst formation and trabecular abnormalities (disorganization, thinning, remodelling) were also observed in areas of abnormal signal intensity. Increased bone density because of trabecular thickening induced a decrease in signal in all sequences.

Bone marrow necrosis

A 64-year-old woman was admitted with a high fever and generalized bone pain. There was systemic lymphadenopathy and hepatosplenomegaly. Laboratory examination showed pancytopenia and high levels of lactate dehydrogenase (13 087 U/l) and alkaline phosphatase (1576 U/l). Bone marrow aspiration from both the sternum and iliac crest yielded necrotic marrow with smudge cells in a background of acidophilic granular material (top left, Wright’s stain). A section of the marrow clots showed shadows of cells with dimly stained nuclei that were reminiscent of tumour cells (bottom left, haematoxylin and eosin). In view of the severity of the illness, combination chemotherapy (cyclophosphamide, vincristine, methotrexate, prednisolone and procarbazine) was immediately started. This resulted in rapid regression of the organomegaly. However, after 1 month, lymph nodes began to regrow with 40% lymphoma-like cells in the peripheral blood. Lymph node biopsy was scheduled but the patient died of intracranial haemorrhage. Postmortem examination showed T-cell lymphoma involving many organs including the bone marrow. Bone marrow necrosis persisted multifocally with areas of intact lymphoma cells (right, haematoxylin and eosin). Bone marrow necrosis is a grave prognostic sign, as most cases are associated with either haematologic malignancy or metastatic cancer. It is likely that the expansive growth of tumour cells within the non-compliant space impedes blood flow, causing ischaemic necrosis of the marrow.

Bone Marrow Necrosis: A Rare Complication of Herbal Treatment with Hypericum Perforatum (St. John’s Wort)

A 22-year-old man presented with fever and ulceration of the oral mucosa. The patient had pharyngeal and esophageal candidiasis. For the 3 weeks prior to presentation, he had been taking approximately 1000 mg/day of flowering herbs (Hypericum perforatum L, known as St. John's wort) for treatment of depression. A complete blood count on the first day of hospitalization showed agranulocytosis and normocytic anemia. His condition worsened, and he developed progressive dysphagia. A bone marrow biopsy on day 3 revealed bone marrow necrosis. After the diagnosis was established (day 3 of hospitalization), treatment with granulocyte colony-stimulating factor 48 U/day, intravenous immunoglobulin 400 mg/kg, and amphotericin B 100 mg/day was initiated. The patient did not respond, and died within one week of the diagnosis. This cases suggests that Hypericum species may lead to severe hematologic toxicity, with conditions involving bone marrow necrosis.

Leukemoid Reaction in Association with Bone Marrow Necrosis due to Metastatic Prostate Cancer

An 80-year-old man presented to the internist with fever, fatigue and leukocytosis up to 66.8 x 10(3)/microl. Although a chronic myelogenous leukemia was initially suspected, he was diagnosed as metastatic bone marrow tumor with bone marrow necrosis from primary prostate cancer on the basis of the clinical and pathological findings. The serum concentrations of IL-6 and TNF-alpha were mildly elevated to 65.0 pg/ml and, 54.0 pg/ml respectively. It is probable that these humoral factors were partially responsible for the leukemoid reaction although other factors induced by the bone marrow necrosis with bone marrow metastasis of prostate cancer are also likely involved.

Extensive Bone Marrow Necrosis with Recovery

Extensive Bone Marrow Necrosis with Recovery

Bone marrow necrosis successfully treated with corticosteroid

A 60-yr-old white woman with CREST syndrome (calcinosis cutis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, telangectasia), idiophatic portal hypertension and esophageal varices presented with a 2-month history of bone pain and severe anemia, requiring erythrocyte transfusion every 5-7 d. Initial laboratory findings were hemoglobin (Hb) 4.4 g/dL, platelets 15 x 10(9)/L, white blood cell count (WBC) 2.7 x 10(9)/L. Bone marrow biopsy showed large areas of BMN, and cultures of bone marrow aspirate were negative. The patient was started on intravenous pulse methylprednisolone (1000 mg/d for 3 d) followed by oral prednisone (1 mg/kg/d), and did not require erythrocyte transfusion thereafter. On the 40th day, our patient had Hb 11.6 g/dL, platelets 120 x 10(9)/L, WBC 6.2 x 10(9)/L. Here, we describe the first report of BMN in a patient with CREST syndrome, the first description of successful treatment with intravenous pulse corticosteroid and discuss the possible immune mechanisms involved in the present case.

Bone marrow pathology in AIDS

Bone marrow morphology is frequently abnormal in patients with AIDS. In this study, we reviewed 97 bone marrow biopsies of AIDS patients performed between 1998 and 2000 in the Emı́lio Ribas Institute of Infectology, which is the reference department for HIV. Specific diagnoses were performed in 33 cases. Fungi were observed in eight cases. Five of them were Histoplasma capsulatum, two were Cryptococcus neoformans, and one probably Candida albicans. Acid-fast bacilli were observed in 12 bone marrow biopsies, three of which were diagnosed to have no mycobacteriosis clinically. Foci of necrosis with clusters of macrophages without any well-formed granuloma were observed in nine cases and well-formed granuloma in three cases. Lymphomatous infiltration was observed in four cases of non-Hodgkin's lymphoma and in two Hodgkin's diseases (mixed cellularity). Extensive necrosis of bone marrow was observed in one case of Burkitt's lymphoma. In conclusion, bone marrow biopsy should be performed to elucidate the etiology of cytopenias, secondary infections, and fever of undetermined origin in AIDS patients.

Pathological and immunohistochemical findings in American crows (Corvus brachyrhynchos) naturally infected with West Nile virus.

Twenty-one American crows were identified as being West Nile virus (WNV) infected by WNV-specific reverse transcriptase-polymerase chain reaction (RT-PCR) performed on fresh brain tissue (cerebrum and cerebellum of 16 crows) or by WNV-specific immunohistochemistry of various organs (21 crows). Consistent gross lesions attributable to WNV infection were not detected. Common histological lesions included necrosis of spleen and bone marrow. West Nile virus antigen was consistently detected in heart and kidney (100%). In addition, bone marrow (92%), duodenum (89%), proventriculus (87%), liver (86%), lung (85%), spleen (80%), pancreas (61%), and brain (45%) contained WNV antigen-positive cells. Infected cells included cardiomyocytes; neurons; endothelial cells and vascular smooth muscle cells; hematopoietic cells of bone marrow; and macrophages of spleen, liver (Kupffer cells), and lungs. Epithelial cells of renal tubules, duodenum, pancreas, and proventriculus were also infected. The diagnostic histopathologist should consider WNV infection in crows in the absence of any inflammatory lesions. Immunohistochemistry of heart and kidney is as reliable in detecting WNV infection in American crows as RT-PCR of fresh brain tissue.

Bone Marrow Necrosis

Bone Marrow Necrosis

Hematological, Biochemical and Histological Effects of Prolonged Exposure to 1-Hexane in Albino Rats

N-Hexane is a chemical solvent produced during the cracking and fractional distillation of crude oil and is used widely in industry (paints, varnishes, inks, plastics and rubber). In addition, n-hexane is a major component of benzine and glue which are often sniffed to induce euphoria. The present study aimed to evaluate the effects of prolonged exposure to n-hexane. The experimental animals (albino rats) were dosed with 5 mg/kg n-hexane dissolved in olive oil subcutaneously once daily, 6 days/week for 8 weeks. The hematological findings revealed marked pancytopenia (anemia, leucopenia, thrombocytopenia) which could be attributed histologically to necrosis and diffuse fibrosis in bone marrow. Hexane-induced neurotoxicity was in the form of mild hemorrhage in brain cortex and could explain the marked decrease in locomotor activity among hexane treated group. The lung tissue revealed moderate hemorrhage with lymphocytic and macrophage infiltration. There were patchy areas of focal hepatocellular necrosis. The cardiac muscle revealed fragmentation that could explain derangement of intracellular ions. There was a significant reduction of myocardial contents of magnesium, potassium and zinc in treated group compared to control group that might have influence upon myocardial excitability. The serum concentration of these elements revealed insignificant difference between treated and control groups. The cardiotoxicity and neurotoxicity of n-hexane could explain mortalities encountered among the treated group throughout the study. The results of the study support the guidelines to minimize occupational exposure 10 1-hexane and to fight glue, benzene and other solvent abuse.

Vasculitis Associated with All Trans Retinoic Acid (ATRA) in a Case with Acute Promyelocytic Leukemia

All trans retinoic acid is the drug of choice in the treatment of acute promyelocytic leukemia. But this drug has some side effects, some of which may be life-threatening. Retinoic acid syndrome is the most frequent and dangerous side effect of this differentiation inducing agent. Other side effects include Sweet's syndrome, vasculitis, hypercalcemia, bone marrow necrosis and fibrosis, thromboembolic events, erythema nodosum, granulomatous proliferation and some pulmonary complications. Here, we report vasculitis in a case with APL treated with ATRA and review the literature.

MR-imaging changes of musculoskeletal soft-tissue sarcomas associated with neoadjuvant chemotherapy and hyperthermia

Purpose: To evaluate early changes in musculoskeletal soft-tissue sarcomas under neoadjuvant chemotherapy combined with regional hyperthermia (RHT). Patients and methods: Nineteen consecutive patients with high-grade soft-tissue sarcomas of the musculoskeletal system were treated with neoadjuvant chemotherapy combined with RHT. Patients were imaged, using a high field MR-scanner, before onset of therapy, immediately after one and after four cycles of therapy. The images were evaluated for volume reduction and development of tumour necrosis. In addition, side effects such as surrounding soft-tissue oedema, bleeding and muscle or bone marrow necrosis were analysed. Results: Tumour volume reduction was significant after the completion of neoadjuvant therapy (mean 49%, range 5-91%; ( p < 0.001). Extent of tumour necrosis was also significantly different before (mean 22%) and after therapy (mean 58%, p < 0.001). Three patients showed strong tumour necrosis already after one cycle of treatment. Tumour volume reduction was not associated with the extent of pre-existing necrosis or necrosis development. The extent of tumour volume before start of therapy did not affect volume reduction or necrosis induction after therapy. Reduction of tumour oedema was significant after therapy ( p < 0.001). No side effects were observed during thermochemotherapy. Conclusion: Neoadjuvant chemotherapy combined with RHT resulted in significant tumour volume reduction and induction of tumour necrosis, which can be detected early and monitored closely with MRI.

Letter to the Editor

Letter to the Editor

283. Different schemes of B-cell chronic lymphocytic leukemia (B-CLL) treatment in population affected by the Chernobyl accident consequences

The aim of the study was to evaluate different schemes of B-CLL therapy in population affected by the Chernobyl nuclear power station accident consequences. The 32 patients with B-CLL were treated in Hematological Department of Research Centre for Radiation Medicine in postaccidental period from 1990 to 2003. 16 men aged 42–74 years with B-CLL were studied. The absorbed dose of ionizing radiation varied from 2.8 to 12 cSv but was defined not for all persons. The treatment was started from 1 to 10 months after B-CLL diagnosis. Before B-CLL treatment the most patients had total increase of lymphatic nodes, splenomegaly, hepatomegaly, toxicopaty syndroms, high frequency of infections complications, severe anemia, thrombocytopenia, hemolytic syndrome, leukocytosis. The monoclonal population of B – lymphocytic was present in bone marrow (BM) in the typical variant of B-CLL. Diffused lymphoid infiltration, forming spots of BM necrosis with moderate resorbtion, fragmentation, lysis was found on hystology of BM threpanobioptat in all patients. B-CLL in clean-up workers of the Chernobyl accident consequences is characterized by rapid progression of the disease, and diffusion defeat of BM. It has been established that the most effective programe of treatment is the combination of fludarabine with cyclophosphamide. The complete and partial remission was achieved in 11 out of 14 cases. The treatment scheme (COP, CHOP, leukerane with prednisolone) did not led to complete remission. Our results of B-CLL treatment showed the high effectiveness of fludarabine-based therapy.

Bone marrow necrosis in non-hodgkin’s lymphoma

We describe a newly diagnosed case of non-Hodgkin’s lymphoma with clinical and haematological features of bone marrow necrosis in a three-year old female who sustained a rapidly progressive and terminal course

Bone tissue ablation with sub-microS pulses of a Q-switch CO(2) laser: histological examination of thermal side effects.

. The goal of this study is an in vitro evaluation of thermal side-effects by the application of short sub- micro s CO(2) laser pulses in combination with an air-water spray on different types of bone tissue. A mechanically Q-switched CO(2) laser delivered 300 ns pulses at 9.6 micro m wavelength, which were focused down to a spot size of 440 micro m on the tissue (a corresponding energy density of 9 J/cm(2)). Bone samples (blocks from pig femur, rib, or cartilage) were moved through the beam repeatedly until 1-5 mm deep cuts were produced. An air driven water spray was applied to prevent the tissue dehydration. Subsequent visual and histological examinations revealed no carbonisation, melting traces or fissuring of the tissue. An extremely narrow, 2-6 micro m thick thermally altered layer was observed at the cut border in compacta and cartilage. No accumulation of the thermal damage occurred with increasing cut depth. Laser incisions in trabecular tissue were accompanied with a 100-200 micro m thick zone of thermal necrosis in bone marrow. The difference from compacta and cartilage can be explained considering the particular character of the spreading of the ablation products in the trabecular meshwork. Minor thermal side effects make the Q-switched and probably other short pulsed CO(2) laser systems interesting for hard tissue surgery.

Atypical blasts and bone marrow necrosis associated with near-triploid relapse of acute promyelocytic leukemia after arsenic trioxide treatment

The pathologic features of acute promyelocytic leukemia (APL) with t(15;17)(q22;q21) are highly characteristic, which with few exceptions enable a firm diagnosis to be made on morphologic grounds. An APL patient in first relapse presented with large, bizarre circulating blasts and bone marrow necrosis 2 weeks after chemotherapy consolidation for an arsenic trioxide–induced remission. Although a morphologic diagnosis could not be reached, cytogenetic investigations showed a near-triploid clone with t(15;17), confirming APL in second relapse. This case showed that clonal evolution with additional karyotypic aberrations might alter the blast morphology and pathologic features in APL. HUM PATHOL 33:849-851. Copyright 2002, Elsevier Science (USA). All rights reserved.

Bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in five painted storks

Five painted storks were treated with fenbendazole for 5 days for internal parasitism. Four birds died following treatment. Profound heteropenia was a consistent finding in all samples evaluated; additionally, the 1 surviving bird had progressive anemia. Consistent necropsy findings in the 4 birds that died were small intestinal crypt cell necrosis and severe bone marrow depletion and necrosis. Fenbendazole has been associated with bone marrow hypoplasia and enteric damage in mammals and other species of birds. The dosages of fenbendazole used in birds are often substantially higher than those recommended for mammals, which may contribute to bone marrow hypoplasia and intestinal crypt cell necrosis associated with fenbendazole administration in birds.

Bone marrow necrosis: clinicopathologic analysis of 20 cases and review of the literature.

Bone marrow necrosis (BMN) is a relatively uncommon clinicopathologic entity. The etiology is diverse, and malignancy, especially hematopoietic in origin, is the most common underlying disease of BMN. In this retrospective analysis, cases with BMN were re-evaluated for etiology, histopathologic details, and clinical manifestations. In the last 8 years, 23 cases of BMN were detected among the 1,083 bone marrow (BM) biopsies, and the prevalence was found to be 2.2%. Three of these 23 cases with BMN were children, and 20 cases were in adults. Sixteen of these cases (80%) had underlying malignant disease, and four (20%) had nonmalignant disease. Among the malignant cases, three cases had acute myeloblastic leukemia (AML), four had relapsed Hodgkin's disease (R-HD), one had acute lymphoblastic leukemia (ALL), two had chronic myelocytic leukemia (CML), two had non-Hodgkin's lymphoma (NHL), three had disseminated intravascular coagulation (DIC) associated with metastatic solid tumor, and one had myelodysplastic syndrome/myeloproliferative syndrome (MDS/MPS). Among the nonmalignant cases, two had tuberculosis infection, one had anti-phospholipid syndrome (APS), and one had a history of drug ingestion. The most common symptoms were bone pain, fever, fatigue, and jaundice. The most common laboratory findings were variable and associated with underlying disease, but anemia, leukopenia, thrombocytopenia, and high LDH and alkaline phosphatase levels were detected in the majority of the cases, as was also seen in other series. BMN was graded according to the extent of necrosis in the BM biopsy, and necrosis was extensive in 12 cases, moderate in five cases, and mild in three cases. Increased reticulin was found in 16 cases; four cases had severe, eight had moderate, and four had mild fibrosis, and this was found to be an interesting accompanying finding in BMN. In conclusion malignancy is the most common cause of BMN but some nonmalignant conditions such as tuberculosis and APS may be the underlying cause of BMN.