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[The morphological assessment of bone marrow infiltration in neuroblastoma].

Bone marrow biopsy is very important in diagnosis and follow-up of children affected by neuroblastoma (NB). Between June 1995 and May 1997 we studied 55 patients with NB stage 4. Specimens were obtained at the diagnosis (in 8 patients) and after chemotherapy (in 55 patients) in order to evaluate the effects of treatment on bone marrow disease. 88% of 343 biopsies were representative versus 99% of 639 aspirates. Of 8 stage 4 patients evaluated at diagnosis, 15/16 biopsies versus 9/15 aspirates were positive. Following chemotherapy, out of 298 evaluable sites examined, 111 biopsies versus 30 aspirates (37 versus 10%) were positive. Of 111 positive biopsies 53 showed a focal pattern (35 differentiated, 18 undifferentiated), while 51 showed a diffuse pattern (18 differentiated, 40 undifferentiated). Our results confirm previous literature data indicating a better efficacy of histology versus morphology in detecting residual bone marrow disease (especially in case of focal differentiated pattern). The recent introduction of a specific monoclonal antibody, called anti-GD2, has improved our capacity to detect minimal residual disease in patients' bone marrow. The inclusion of anti-GD2 immunohistochemistry in our evaluation will possibly increase our overall sensitivity to detect minimal residual disease and may provide information capable to direct the physician's decision into a more rational patient's treatment.

Adolescent↗

Whole-body MRI in the detection of bone marrow infiltration in patients with plasma cell neoplasms in comparison to the radiological skeletal survey.

To compare the diagnostic value of whole-body MRI versus radiological skeletal survey (RSS) in staging patients with plasma cell neoplasms (PCN) and to evaluate the possible therapeutic impact of the replacement of RSS by whole-body MRI. Fifty-four patients with PCN [multiple myeloma (MM), n=47; monoclonal gammopathy of unknown significance (MGUS), n=7] were studied by whole-body MRI and RSS in a monocenter prospective analysis from August 2002 to May 2004. The MRIs were performed using a rolling table platform "AngioSURF" for unlimited field of view with a 1.5-T system (Magnetom Sonata/Maestro Class, Siemens Medical Solutions, Erlangen, Germany). A coronal STIR sequence (TR5500-4230/TE102-94/TI160) was used for imaging of the different body regions, including the head, neck, thorax, abdomen, pelvis and upper and lower extremities. The RSS consisted of eight different projections of the axial and appendicular skeleton. In 41/54 (74%) patients, the results of the whole-body MRI and RSS were concordant. In 11/54 (20%) patients, both imaging techniques were negative. Bone involvement was observed in 30/54 (55%) patients; however, whole-body MRI revealed this more extensively than the RSS in 27/30 (90%) patients with concordant positive imaging findings. In 3/30 (10%) patients, both imaging techniques demonstrated a similar extent of bone marrow infiltration. In 10/54 (19%) patients, the whole-body MRI was superior to RSS in detecting bone marrow infiltration, whereas the RSS was negative. In 3/54 (6%) patients, the RSS was proven to be false positive by the clinical course, whereas the whole-body MRI was truly negative. Whole-body MRI is a fast and highly effective method for staging PCN patients by the use of a rolling table platform. Moreover, it is more sensitive and specific than RSS and reveals bone marrow infiltration and extensive disease more reliably. Therefore, whole-body MRI should be performed as an additional method of exactly staging PCN patients and - with more data in the field - may even prove to be an alternate and more sensitive staging procedure than RSS in PCN patients.

Adult↗

Clinically unsuspected Hodgkin disease presenting initially in the bone marrow of patients infected with the human immunodeficiency virus.

BACKGROUND: Hodgkin disease (HD) in patients infected with the human immunodeficiency virus (HIV) is an aggressive neoplasm that often exhibits high stage and extranodal involvement at the time of presentation. Because of the propensity of HIV-associated HD to involve the bone marrow early in the course of the neoplasm, bone marrow examination may often represent the initial source for the diagnosis. In most cases, however, there is a clinical suspicion of HD before bone marrow examination. METHODS: Three cases are presented in which HD was not clinically suspected and the initial diagnosis of the neoplasm was suggested by atypical lymphohistiocytic lesions identified on routine bone marrow examination, later to be confirmed by lymph node biopsy. RESULTS: In none of the cases was HD clinically suspected before bone marrow examination; in two cases, fever was the only clue that the patients may have HD. It was found on bone marrow biopsy that all three patients had lymphohistiocytic aggregates with large atypical mononuclear cells suggestive but not diagnostic of HD. CONCLUSIONS: Bone marrow examination may provide the initial evidence of HD in HIV-infected patients, even when there is little or no clinical indication of the neoplasm.

Acquired Immunodeficiency Syndrome↗

The bone marrow in human immunodeficiency virus (HIV)-related disease. Morphology and clinical correlation.

To determine the true incidence of abnormalities in bone marrow specimens from patients infected with human immunodeficiency virus (HIV) and the clinical significance of these abnormalities regarding their cause and their role in the production of hematologic complications, 216 bone marrow biopsies, aspirates, and/or imprint preparations from 178 patients who either were seropositive for HIV infection or met the Centers for Disease Control (CDC) criteria for acquired immunodeficiency syndrome (AIDS) were studied. Detailed morphologic review was performed in a blind fashion as to clinical status. Extensive clinical, therapeutic, and laboratory data were collected for each patient. Statistical analysis was performed to detect significant correlations between morphologic findings and clinical/therapeutic/laboratory features. Among the most common bone marrow findings were hypercellularity (53% of specimens), myelodysplasia (69%), evidence of reticuloendothelial (RE) iron blockade (65%), megaloblastic hematopoiesis (38%), fibrosis (20%), plasmacytosis (25%), lymphocytic aggregates (36%), and granulomas (13%). A number of statistically significant correlations between morphologic findings and clinical features were noted. No significant association was detected between any morphologic finding and therapy with a variety of drugs. In 7 of 14 (50%) patients found to have marrow involvement by malignant neoplasm, the bone marrow represented the initial site of diagnosis of the neoplasm. Most of the bone marrow abnormalities associated with HIV infection appear to be related directly to the infection or its complications and not to therapeutic intervention. In certain clinical situations, bone marrow examination continues to be useful in the management of patients infected with HIV.

Adolescent↗

Search for proviral simian sarcoma associated virus sequences in bone marrow cells from children with neoplasms of mesenchymal origin.

DNAs obtained from bone marrow cells of 31 children with neoplasms of mesenchymal origin were tested for the presence of proviral simian sarcoma associated virus by southern blot-hybridization. The lower limit of detection in this method was one provirus per 20-30 cells. Applying stringent conditions of hybridization, no proviral DNA could be detected in any of the samples tested, most of which were from children with leukemia or with bone marrow invading lymphosarcomas. Relaxed conditions of hybridization revealed a diffuse pattern of hybridizing fragments which was similar in all DNAs tested, including normal human DNA.

Bone Marrow↗

Recent advances in bone marrow scanning.

Interest in bone marrow scanning has been renewed as the result of the development of radiopharmaceuticals for evaluating specific aspects of bone marrow anatomy, physiology and pathology. This article provides a brief review of bone marrow structure, blood flow and function essential to the understanding of basic principles of bone marrow radionuclide imaging. The prospects and limitations of imaging haematopoietic bone marrow in man using indium 111 chloride, technetium-99m (99mTc)-labelled microcolloid or 99mTc-labelled monoclonal antigranulocytic and antimyelocytic antibodies are discussed in more detail. The technical aspects of bone marrow scintigraphy are presented. Results of more recent studies evaluating bone marrow scanning in circulatory, inflammatory and in systemic haematological disorders are summarized. Special attention is paid to the concept of bone marrow micrometastases and its implications for the follow-up of patients with malignant tumours. Recent results suggest that immunoscintigraphy of bone marrow may provide a novel and sensitive approach for establishing the presence and extent of bone marrow infiltration.

Antibodies, Monoclonal↗

p27(Kip1) immunostaining for the differential diagnosis of small b-cell neoplasms in trephine bone marrow biopsies.

The distinction between mantle cell lymphoma (MCL) and other small B-cell non-Hodgkin lymphomas (NHL) is important because MCL has a more aggressive clinical course. In bone marrow (BM) biopsy specimens, this distinction can be particularly difficult. Although cyclin D1 immunostaining and molecular detection of the t(11;14) translocation are highly specific markers for MCL, they fail to detect a proportion of cases. We have recently described that MCL typically lacks detectable expression of the cyclin-dependent kinase inhibitor p27(kip1) protein by immunostaining, which is expressed at high levels in most small B-cell NHL inversely correlated to the proliferation rate. We therefore examined whether p27(kip1) immunostaining could be a useful adjunct for the differential diagnosis of small B-cell NHL infiltrates in the BM. Trephine BM biopsy specimens of 96 patients, including well-characterized MCL (19 cases), B-cell chronic lymphocytic leukemia (27 cases), follicular lymphoma (18 cases), hairy cell leukemia (22 cases), and marginal zone lymphoma (10 cases) as well as 10 reactive BM, including five with benign lymphoid aggregates were investigated. In addition, the presence of a t(11;14) translocation involving the major translocation cluster was studied by PCR in all MCL. All cases of B-cell chronic lymphocytic leukemia, follicular lymphoma, and marginal zone lymphoma revealed a strong p27(kip1) nuclear staining in the majority of neoplastic cells. Fourteen (78%) cases of MCL were p27(kip1)-negative in the tumor cells, whereas four cases revealed a weak nuclear positivity. Seventeen (77%) cases of hairy cell leukemia were also either completely negative for p27(kip1) or showed a faint positive staining in a minority of the neoplastic cells. Nine of 19 cases (47%) of MCL showed a bcl1 rearrangement involving the major translocation cluster region. These findings demonstrate that p27(kip1) immunostaining is a valuable additional marker for the differential diagnosis of small B-cell NHL infiltrates in BM biopsies. The reduction or lack of p27(kip1) protein expression in MCL, as well as in hairy cell leukemia, might be an important event in the pathogenesis of these disorders.

Biopsy↗