Diffuse Bone Marrow Research Articles

Differential Diagnosis of Pedal Osteomyelitis and Diabetic Neuroarthropathy: MR Imaging

Almost all diabetic foot infections originate from a foot ulcer. Decreased pain perception and structural deformities such as previous partial foot amputation, Charcot joints, and toe deformity in combination with chronic ischemia lead to a propensity for skin breakdown and subsequent infection. Magnetic resonance (MR) imaging is increasingly performed to evaluate for potential bone infection, but diagnosis of osteomyelitis can be complicated because signal changes from acute Charcot arthropathy, fractures, and postoperative residues may be mistaken for infection. Signal alterations of bone infection may be atypical in sclerosing osteomyelitis and gangrene. Differentiation between osteomyelitis and acute or subacute neuroarthropathy requires careful analysis of the location of bone signal alterations, their distribution, and pattern because qualitative changes are often identical. Presence of secondary signs such as adjacent ulcer, cellulitis, and sinus tract is indicative of osteomyelitis. Differentiation of noninfected neuroarthropathy from infected neuroarthropathy based on MR examinations is difficult. Presence of a sinus tract, disappearance of subchondral cysts, diffuse bone marrow abnormality, and bone erosions are in favor of infection.

In vitro chemosensitivity to gemcitabine, oxaliplatin and zoledronic acid predicts treatment response in metastatic gastric cancer - a case report

2122 Background: Individual response of disseminated cancer to chemotherapy is unpredictable. In vitrochemotherapy induced apoptosis can be measured and might be a method to evaluate in vivoactivity of tested drugs. Methods: In this report, tumor cells of a patient with signet-cell carcinoma of the stomach and diffuse bone marrow infiltration were cultured and tested for in vitrochemosensitivity. Tumour cells were selected by a ficoll gradient, cultured and incubated with cytotoxic agents in various concentrations and combinations for 24 hours. The percentage of apoptotic cells was assessed by flow-cytometry using Annexin V. Results: The drugs gemcitabine, oxaliplatin and zoledronic acid were found to induce in vitrotumor cell apoptosis synergistically. According to the results of the in vitro chemosensitivity testing, the patient started a combination chemotherapy with a fixed-dose rate regimen of gemcitabine (1000 mg/m2 as a 10 mg/m2/min infusion on day 1) and oxaliplatin (100 mg/m2 as a 2-hour infusion on day 2), which was repeated every 2 weeks. Additionally, the patient received a biweekly infusion of the bisphosphonate zoledronic acid (4 mg, day 1). An initially existing disseminated intravascular coagulopathy quickly resolved, and after 6 months of treatment a still lasting complete response was induced, thus confirming the results of in vitrochemosensitivity testing. Conclusions: In vitrochemosensitivity testing might be very helpful to predict chemotherapy response in selected patients with metastatic gastric cancer. No significant financial relationships to disclose.

Beurteilbarkeit diffuser Knochenmarksinfiltrationen der Wirbelsäule bei multiplem Myelom: Korrelation von MRT-Befunden mit der Histologie

To determine the detection of diffuse bone marrow infiltration with MRI in comparison with histopathological findings. MRI was performed on 45 patients with histologically proven multiple myeloma and on 30 healthy individuals. Three experienced radiologists read separately Tl-weighted SE sequences, STIR sequences and the combination of Tl-weighted SE and STIR sequences of the spine. Additionally, Tl-weighted SE sequences were obtained after gadolinium administration and the percentage increase in signal intensity was calculated. Bone marrow histology was used as gold standard for assessing the grade of infiltration. A dichotomous decision (infiltration yes/no) was made when assessing the MRI examinations. For the visual detection of diffuse infiltration, the best sensitivity was found with Tl-weighted SE sequences, achieving 71 % on average. The specificity was 89 %. The STIR sequences showed a sensitivity of 61 % and a specificity of 98 %, and the combination of Tl-weighted/STIR-sequences achieved a sensitivity of 65 % and a specificity of 94 %. In comparison with the histological findings, the sensitivity of the Tl-weighted sequences was 35 % for low-grade, 89 % for moderate and 100 % for high-grade infiltration. The application of contrast material with calculation of the percentage signal increase improved the detection by 7 %. The sensitivity of the visual detection of diffuse multiple myeloma with unenhanced MRI is limited for low-grade or moderate infiltration, whereas the sensitivity for high grade infiltration is reliable. The specificity is high and the diagnostic confidence improves after application of contrast material with calculation of the percentage increase in signal intensity.

Metastatic malignant melanoma presenting as pancytopenia in a three‐year‐old boy

Malignant melanoma is rare in childhood and has never been reported to cause pancytopenia due to bone marrow metastases in a child. We report a 3-year-old boy with a large congenital melanocytic nevus who presented with bone pain and pancytopenia due to diffuse bone and bone marrow infiltration with metastatic melanoma without an identifiable primary site. Despite treatment with imatinib mesylate there was no response and the patient died with progressive disease. This case illustrates an unusual presentation of bone marrow failure secondary to malignant melanoma in a young child with symptomatic metastatic marrow infiltration, a rarely reported site of melanoma involvement in adults or children.

In vitro chemosensitivity to gemcitabine, oxaliplatin and zoledronic acid predicts treatment response in metastatic gastric cancer

Individual response of disseminated cancer to chemotherapy is unpredictable. In vitro chemotherapy-induced apoptosis can be measured and might be a method to evaluate in vivo activity of tested drugs. In this report, tumor cells of a patient with signet cell carcinoma of the stomach and diffuse bone marrow infiltration were cultured and tested for in vitro chemosensitivity. The drugs gemcitabine, oxaliplatin and zoledronic acid were found to induce in vitro tumor cell apoptosis synergistically, and subsequently were used as combination chemotherapy regimen. An initially existing disseminated intravascular coagulopathy quickly resolved and after 6 months of treatment on ongoing complete response was induced, thus confirming the results of in vitro chemosensitivity testing.

Primary multifocal osseous Hodgkin disease: a case report and review of the literature

Hodgkin disease (HD) typically involves the lymphatic system at one or more sites. Rarely, Hodgkin disease presents as an osseous lesion without involvement of lymph nodes. Therefore, the histologic diagnosis of osseous HD can be problematic. We present a rare case of multifocal osseous HD and a review the literature with special emphasis on treatment and prognosis. Osteomyelitis and lymphoma are the main differential diagnoses and can only be excluded histologically by the presence of Sternberg Reed cells or by immunohistochemical examinations. This case reports a 21-year old man with a Hodgkin lymphoma located at the proximal femur and the proximal tibia. Staging studies revealed no other tumor manifestations. Regarding the Ann Arbor classification, the presented case should be a stage IV disease. The patient is without evidence of disease 4 years after curettage, local radiation therapy, and systemic chemotherapy despite the poor prognosis considering the Ann Arbor classification. Reviewing the few reported cases, osseous HD must be distinguished from systemic HD with diffuse bone marrow involvement and from osseous metastases in advanced stage of disease because it seems to have a better prognosis.

Identical Novel C-Kit Transcripts in Two Patients with Mast Cell Leukemia.

Background: Mutations of c-kit have been well documented in mast cell neoplasms. The most common alterations found in human cutaneous and systemic mastocytosis are V560G and D816V. Mast cell leukemia is the most aggressive mast cell neoplasm, characterized by diffuse bone marrow and peripheral blood involvement. It has not been well studied due to its rarity. To date, no C-KIT mutational analysis of primary mast cell leukemia cells has been reported, although a mast cell leukemia cell line expresses the V560G and D816V mutations. Here we report on C-KIT cDNA analysis on two patients diagnosed with mast cell leukemia at the University of Chicago Hospitals. Both patients had peripheral blood involvement. Their diagnosis was confirmed on bone marrow biopsies with tryptase stains. Patient 1, diagnosed in 1989, died shortly after diagnosis. Patient 2 achieved a complete remission with allogeneic stem cell transplant. Upon relapse, treatment with Gleevec, resulted in an incomplete but significant response. This patient eventually died of sepsis following refractory cytopenias.Methodology:We retrieved liquid nitrogen frozen, pre-treatment bone marrow aspirate samples from both patients. We performed RT-PCR analysis of the entire coding region of C-KIT by amplifying 21 exons in smaller fragments. Each PCR product was cloned and sequenced. A thorough sequencing analysis was performed by screening several clones of each amplification product, with the purpose of being able to identify low abundance transcripts.Results: In both patients, the most abundant transcript was alternatively spliced and lacked exons 12 and 13. In addition, coexisting on the same allele, there were novel but not identical single amino acid deletions: deletion of L521 in patient 1 and of S715 in patient 2. A second novel alteration detected in both patients was the duplication of Q252. Patient 2 also demonstrated two independent, low abundance transcripts, one encoding the point mutation V559G and the other containing a deletion of exon 12.Discussion: Here we describe two novel and identical C-KIT alterations in two patients with mast cell leukemia (deletion of exons 12 and 13 and duplication of Q252). We hypothesize that both are key molecular changes underlying mast cell leukemia. Exons 12 and 13 encode the N-terminus of the kinase domain, which is thought to have modulatory effect on the kinase active site. Amino acid 252 is located in the fourth immunoglobulin-like domain of the extracellular region, which is thought to be critical for receptor dimerization and phosphorylation. We predict that these mutations result in the superactivation of C-KIT, based on the aggressive behaviour of mast cell leukemia. The response to Gleeevec seen in patient 2 indicates that at least some of these transcripts are Gleevec sensitive. Functional assays to test if the encoded C-KIT proteins are constitutively activated and whether Gleevec inhibits the novel C-KIT proteins are in progress.

Neovascularization of bone marrow in patients with diffuse multiple myeloma

The goal of the current study was to assess the correlation between bone marrow histology and contrast enhancement in infiltrative diffuse myeloma. Forty-four patients with homogeneous diffuse infiltration of bone marrow by multiple myeloma were examined using magnetic resonance imaging of the spine. The sequence protocol included T1-weighted spin-echo (pre- and post-gadolinium dimeglumine administration) and short-inversion time inversion recovery sequences. The percent increase in signal after intravenous gadolinium administration was calculated in bone marrow from patients with myeloma and from a control group of 86 patients who did not have bone marrow disease. Grade of infiltration with plasma cells, fat cell content, and hematopoietic marrow content were evaluated via histologic assessment of bone marrow, and microvessel density was evaluated via anti-CD34-positive immunostaining. Increased microvessel density was observed in association with increasing plasma cell content (Kruskall-Wallis test: P < 0.0001). Contrast enhancement increased in a stepwise manner according to grade of microvessel density (Mann-Whitney U test: P < 0.05 and P < 0.001 for increases from low to intermediate and intermediate to high grade) and was significantly higher in patients with myeloma compared with control patients (Mann-Whitney U test: P < 0.001). A significant correlation also was found between histologic extent of tumor infiltration and contrast enhancement (Mann-Whitney U test: P < 0.0001). The mean level of contrast enhancement was 18% in the control group, 26% in patients with low-grade infiltration, 49% in patients with intermediate-grade infiltration, and 90% in patients with high-grade infiltration. In addition, fat cell content was found to be inversely correlated with contrast enhancement (chi-square test: P < 0.01). As a consequence of increased microvessel density, decreased fat cell content, and increased cellularity, the presence of diffuse bone marrow infiltration in patients with multiple myeloma can be verified using gadolinium-enhanced magnetic resonance imaging.

Presentation of Extramedullary Acute Myelogenous Leukemia as Bilateral Testicular Masses: Response to Non-Myeloablative Allogeneic Transplantation

We present an unusual case of extramedullary acute myelogenous leukemia (AML) presenting as bilateral testicular masses. The patient subsequently developed diffuse skin lesions and bone marrow involvement. Although he had only a partial response to intensive chemotherapy, the patient obtained a complete remission after non-myeloablative allogeneic transplantation.

Confirmation of the Activity of the Interleukin-2 Fusion Toxin Denileukin Diftitox against Chemorefractory Chronic Lymphocytic Leukemia, including Cases with Chromosome 17p Deletions and without Detectable CD25 Expression

Confirmation of the Activity of the Interleukin-2 Fusion Toxin Denileukin Diftitox against Chemorefractory Chronic Lymphocytic Leukemia, including Cases with Chromosome 17p Deletions and without Detectable CD25 Expression

Diffuse Bone Marrow Uptake on Whole-Body F-18 Fluorodeoxyglucose Positron Emission Tomography in a Patient Taking Recombinant Erythropoietin

F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) is used extensively in oncology to diagnose, stage, and restage patients with various malignancies. Many patients treated for malignancies develop neutropenia secondary to marrow suppressive chemotherapy and are subsequently treated with synthetic hematopoietic growth factors (HGF), both granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-colony-stimulating factor (G-CSF). Patients taking HGF can present a diagnostic challenge for those interpreting PET because they can demonstrate diffuse marrow uptake on FDG-PET scans, mimicking diffuse bone marrow metastases. It has not been reported whether bone marrow uptake is affected on PET scans in patients taking erythropoietin, the erythroid-specific cell-line stimulator. We report a case of extensive diffuse bone marrow uptake in a 77-year-old man with a history of colon cancer who began taking erythropoietin 3 weeks before his PET scan. This case demonstrates the need to consider erythropoietin in the differential diagnosis of possible etiologies causing diffuse bone marrow uptake on PET scans.

Bone marrow with diffuse tumor infiltration in patients with lymphoproliferative diseases: dynamic gadolinium-enhanced MR imaging.

To evaluate gadolinium enhancement of bone marrow in patients with lymphoproliferative diseases and diffuse bone marrow involvement. Dynamic contrast material-enhanced magnetic resonance (MR) imaging of the thoracolumbar spine was performed in 42 patients with histologically proved diffuse bone marrow involvement and newly diagnosed myeloma (n = 31), non-Hodgkin lymphoma (n = 8), or Hodgkin disease (n = 3). The maximum percentage of enhancement (Emax), enhancement slope, and enhancement washout were determined from enhancement time curves (ETCs). A three-grade system for scoring bone marrow involvement was based on the percentage of neoplastic cells in bone marrow samples. Quantitative ETC values for the 42 patients were compared with ETC values for healthy subjects and with grades of bone marrow involvement by using mean t test comparisons. Receiver operating characteristic (ROC) analysis was conducted by comparing Emax values between patients with and those without bone marrow involvement. Baseline and follow-up MR imaging findings were compared in nine patients. Significant differences in Emax (P <.001), slope (P <.001), and washout (P =.005) were found between subjects with normal bone marrow and patients with diffuse bone marrow involvement. ROC analysis results showed Emax values to have a diagnostic accuracy of 99%. Emax, slope, and washout values increased with increasing bone marrow involvement grade. The mean Emax increased from 339% to 737%. Contrast enhancement decreased after treatment in all six patients who responded to treatment but not in two of three patients who did not respond to treatment. Dynamic contrast-enhanced MR images can demonstrate increased bone marrow enhancement in patients with lymphoproliferative diseases and marrow involvement.

MRI of joint fluid in femoral head osteonecrosis.

To evaluate the relationship between joint fluid, intramedullary pressure (IMP), bone marrow edema, and stages of osteonecrosis of the femoral head (ONFH). We reviewed the magnetic resonance (MR) images of 28 patients with 40 documented ONFHs. IMP was measured in 16 symptomatic hips. The amount of joint fluid was graded as 0 (no fluid), 1 (fluid <5 mm in width), or 2 (fluid > or = 5 mm in width) adjacent to the entire length of the femoral neck. Associated focal and diffuse bone marrow abnormalities were evaluated. A control group of 29 recruited individuals without symptoms related to hip disease were examined. Follow-up MR images were obtained in four patients (five affected hips) 6-10 months after core decompression. Of the 40 affected hips, the severity of ONFH was divided into stages 0 (n=4), I (n=28), and II (n=8 hips) on MR findings. The correlation of joint fluid to IMP and to the presence of bone marrow edema was poor. The amount of joint fluid correlated significantly with the stage of ONFH. None of the five affected hips showed decreased joint fluid on follow-up MR images. The amount of joint fluid correlates well with the stage of ONFH. The amount of joint fluid does not correlate with IMP or bone marrow edema.

Technetium-99m-tetrofosmin scintigraphy in patients with metastatic soft tissue sarcoma

The lipophilic cationic compound Tc-99m-tetrofosmin has been demonstrated to be a valuable tool for the detection of a variety of tumours. Tc-99m-tetrofosmin uptake by sarcomas in vitro as well as in primary tumours has been reported. Data on the visualisation of metastatic soft tissue sarcomas using this tracer are missing so far. Ten consecutive patients with histopathologically verified metastatic soft tissue sarcoma were included in the present study. Five patients had previously received cytotoxic treatment, the other five patients were chemonaive. All patients underwent whole body planar examination after administration of 500-550 MBq Tc-99m-tetrofosmin, and in case of lung metastases on CT scan, SPECT images were carried out. Non-physiological accumulation of the tracer was considered as a positive result. Scintigraphic results were compared to conventional imaging by means of MRI/CT scanning. Visualisation of distant metastases was achieved in five patients all of whom were chemonaive, while in the chemotherapeutically pretreated patient group (n=5) false negative results were seen. Progressive disease was confirmed by follow-up in all patients. Pulmonary metastases were visualised only in SPECT acquisition and not on planar images. In one patient with diffuse bone marrow infiltration (inflammatory myofibroblastic sarcoma) Tc-99m-tetrofosmin scintigraphy was positive, while CT showed a negative result. According to our results, detection of metastatic soft tissue sarcomas by Tc-99m-tetrofosmin scintigraphy was strongly dependent on the history of previous treatment of the patient. A positive finding before initiation of chemotherapy was not indicative for subsequent therapeutic response. In the staging of chemonaive patients with metastatic soft tissue sarcoma Tc-99m-tetrofosmin may provide some additional information.

Iron-oxide-enhanced MR imaging of bone marrow in patients with non-Hodgkin's lymphoma: differentiation between tumor infiltration and hypercellular bone marrow.

The aim of this study was to differentiate normal, hypercellular, and neoplastic bone marrow based on its MR enhancement after intravenous administration of superparamagnetic iron oxides in patients with cancer of the hematopoietic system. Eighteen patients with cancer of the hematopoietic system underwent MRI of the spine before and after infusion of ferumoxides ( n=9) and ferumoxtran ( n=9) using T1- and T2-weighted turbo spin-echo (TSE) and short tau inversion recovery sequences (STIR). In all patients diffuse or multifocal bone marrow infiltration was suspected, based on iliac crest biopsy and imaging such as conventional radiographs, MRI, and positron emission tomography. In addition, all patients had a therapy-induced normocellular ( n=7) or hypercellular ( n=11) reconversion of the normal non-neoplastic bone marrow. The MRI data were analyzed by measuring pre- and post-contrast signal intensities (SI) of hematopoietic and neoplastic marrow and by calculating the enhancement as deltaSI(%) data and the tumor-to-bone-marrow contrast as contrast-to-noise ratios (CNR). Changes in bone marrow signal intensity after iron oxide administration were more pronounced on STIR images as compared with T1- and T2-weighted TSE images. The STIR images showed a strong signal decline of normal and hypercellular marrow 45-60 min after iron oxide infusion, but no or only a minor signal decline of neoplastic bone marrow lesions; thus, deltaSI% data were significantly higher in normal and hypercellular reconverted marrow compared with neoplastic bone marrow lesions ( p<0.05). Additionally, the contrast between focal or multifocal neoplastic bone marrow infiltration and normal bone marrow, quantified by CNR data, increased significantly on post-contrast STIR images compared with precontrast images ( p<0.05). Superparamagnetic iron oxides are taken up by normal and hypercellular reconverted bone marrow, but not by neoplastic bone marrow lesions, thereby providing significantly different enhancement patterns on T2-weighted MR images; thus, superparamagnetic iron oxides are useful to differentiate normal and neoplastic bone marrow and to increase the bone marrow-to-tumor contrast.

A case of gastric carcinoma with diffuse bone marrow carcinomatosis showing osteosclerosis

A case of gastric carcinoma with diffuse bone marrow carcinomatosis showing osteosclerosis

Waldenström macroglobulinemia. Development of diagnostic criteria and identification of prognostic factors.

To establish whether a combination of morphologic and immunophenotypic criteria could be developed to more precisely define Waldenström macroglobulinemia (WM) and prognostic factors, we retrospectively assessed the clinical and laboratory features of 111 cases of WM. Bone marrow infiltration by small lymphocytes was documented in each case; and diffuse, interstitial, nodular, and paratrabecular patterns of infiltration were documented in 58%, 32%, 6%, and 4% of cases, respectively. Ninety percent were characterized by a surface immunoglobulin-positive, CD19+CD20+CD5-CD10-CD23- immunophenotype. The median overall survival from diagnosis was 60 months; univariate analysis revealed the following adverse prognostic factors: older than 60 years, performance status more than 1, platelet count less than 100 x 10(3)/microL (< 100 x 10(9)/L), pancytopenia, and diffuse bone marrow infiltration. Associated median survival was 40, 38, 46, 28, and 59 months, respectively. Multivariate analysis revealed age, performance status, and platelet count as prognostically significant, but stratification of patients according to the International Prognostic Index had limited value. We suggest defining WM by the following criteria: IgM monoclonal gammopathy; bone marrow infiltration by small lymphocytes, plasmacytoid cells, and plasma cells in a diffuse, interstitial, or nodular pattern; and a surface immunoglobulin-positive, CD19+CD20+CD5-CD10-CD23- immunophenotype.

Predictive value of technetium-99m sestamibi in patients with multiple myeloma and potential role in the follow-up

Technetium-99m 2-methoxyisobutylisonitrile (99mTc-MIBI or setamibi) has recently been proposed for use in the evaluation of multiple myeloma (MM). The aims of this study were to investigate its potential predictive value in patients with MM and its possible role in the follow-up. Thirty patients with MM who had undergone two 99mTc-MIBI scintigraphic studies at least 2 months apart constituted the study group; 22 of them received chemotherapy in the interval between the two scans. The scans were classified as showing pattern N when only physiological uptake was present, pattern D when diffuse bone marrow uptake was observed, pattern F when areas of focal uptake of the tracer were evident, and pattern F + D when both D and F patterns were observed. Comparative 99mTc-MIBI scintigraphy was considered indicative of disease progression when there was a worsening of the pattern (i.e. from N to D, or from N or D to F or to F + D) or an increase in the pattern D semiquantitative score. It was considered indicative of disease improvement when the opposite trend was observed; otherwise, it was considered to document a stable condition. A significant association was observed between the baseline scintigraphic pattern and clinical status at follow-up in the group of patients evaluated after chemotherapy (chi 2 = 16.7, P < 0.05). A negative baseline 99mTc-MIBI scintigram showed a high predictive accuracy (100%) for remission, while the presence of pattern F or F + D was often associated with a less favourable outcome. A multivariate analysis showed that 99mTc-MIBI uptake pattern has an added value in relation to known prognostic variables such as C-reactive protein. 99mTc-MIBI scintigraphy patterns at follow-up were significantly associated with the clinical status evaluated after chemotherapy (chi 2 = 32.6, P < 0.0001). Considering pattern N as indicating remission, pattern D stable condition, and pattern F or F + D progressive disease, a high concordance between scintigraphic findings and clinical status was found in the 22 patients undergoing chemotherapy (91%). Variation in 99mTc-MIBI findings comparing baseline and follow-up evaluations was significantly associated with clinical status both in patients undergoing chemotherapy (chi 2 = 26.5, P < 0.0005) and in those not undergoing chemotherapy (chi 2 = 8.0, P < 0.005). In conclusion, the results of this study suggest a prognostic value of 99mTc-MIBI scintigraphy in patients with MM and a potential role during the follow-up.

Imaging Of Spinal Infection

MR imaging is the modality of choice for the detection, staging, and differential diagnosis of inflammatory disorders of the spine. Infectious spondylitis is characterized by the involvement of two adjacent vertebrae and the intervening disk with severe BME and early destruction of the end plates. The disk space is narrowed and typically exhibits water-equivalent signal intensity on T2-weighted or STIR images. Prevertebral and epidural extensions, abscess formation, enhancement of the BME, the disk space, and the surrounding granulation tissue are well demonstrated by gadolinium-enhanced images. Cervical spondylitis frequently involves more than one level. Bone marrow abnormalities may be subtle at this level and increased signal intensity of the disk space on T2-weighted or STIR images is an important finding. The risk for neurologic complications is increased. Granulomatous infections caused by tuberculosis, brucellosis, fungi, and parasites, including hydatid disease (Echinococcus), are frequently associated with imaging findings different from those seen with nonspecific bacterial infection. In patients with chronic infectious spondylitis, diffuse reactive bone marrow changes with decreased signal intensity on T1-weighted images, increased signal intensity on T2-weighted and STIR images, and increased uptake after gadolinium administration may occur. This phenomenon is probably caused by reactive bone marrow stimulation, simulating diffuse hematologic neoplastic disease. Erosive intervertebral osteochondrosis with bandlike disk gadolinium enhancement and BME, which is commonly associated with local pain, is the most important differential diagnosis of bacterial spondylitis.

CD38 Expression Correlates with Adverse Biological Features and Predicts Poor Clinical Outcome in B-Cell Chronic Lymphocytic Leukemia

CD38 identifies a surface molecule with multi-functional activity. Its prognostic importance in B-cell chronic lymphocytic leukemia (B-CLL) is currently under investigation in view of the fact that two different groups have recently indicated that CD38 expression could be an independent prognostic marker in B-CLL.We analyzed the clinico-biological features of 61 immunologically typical (CD5+CD23+) B-CLL patients stratified according to the CD38 expression. Twenty-two (36%) patients expressed CD38 in more than 30% of CD19-positive cells and were considered as CD38-positive B-CLL. Atypical morphology (p 0.02), peripheral blood lymphocytosis (p 0.01) and diffuse histopathologic bone marrow pattern (p 0.003) were findings found to be closely associated with CD38 expression. On the other hand, A and B Binet stages (p 0.02) and interstitial bone marrow involvement (p 0.005) were more represented in the CD38-negative B-CLL group. Trisomy 12 was detected more frequently in the CD38-positive B-CLL group, while 13q14 deletions mainly occurred in CD38-negative group (p 0.005). Finally, median survival of CD38-positive B-CLL patients was 90 months, while it was not reached at 180 months in CD38-negative patients.Taken together, our data strongly suggest that the evaluation of CD38 expression may identify two groups patients with B-CLL greatly differing in their clinico-biological features.