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Comparative diagnostic value and therapeutic relevance of magnetic resonance imaging and bone marrow scintigraphy in patients with metastatic solid tumors of the axial skeleton.

PURPOSE: To evaluate the comparative impact of magnetic resonance imaging (MRI) and bone marrow scintigraphy (BMS) in bone marrow metastases of solid tumors. METHODS: In 20 patients with solid tumors MRI of the axial skeleton and whole-body BMS were retrospectively reviewed. Detectability of metastases, extent of disease and therapeutic implications were assessed. RESULTS: In 15/20 (75%) patients MRI and BMS concordantly revealed bone marrow metastases of the axial skeleton. In nine of these 15 patients (60%) MRI showed more metastases. Local radiotherapy or surgery was performed in seven of these cases (78%). BMS detected additional metastases of the appendicular skeleton in 8/15 (53%) patients. In 4/20 cases (20%) the imaging findings were discordant. In three patients with degenerative changes (n=2) or lipoma (n=1) BMS was false positive. In another patient BMS failed to detect metastases proven by MRI and clinical follow-up resulting in subsequent radiation therapy. One patient had normal bone marrow. CONCLUSION: MRI appears to be more sensitive and specific in the detection of bone marrow metastases in the axial skeleton and is of clinical importance for subsequent local therapy.

Bone Marrow Neoplasms↗

Mechanisms, hypotheses and questions regarding prostate cancer micrometastases to bone.

The morbidity and mortality associated with prostate cancer can almost universally be attributed to the consequences of metastases to the bone. While clinically there have been descriptive reports of these lesions and their detection by bone scan, there is an embrrassing paucity of reports as to the mechanisms of prostate cancer cell trafficking to the bone, adaptation to the bone environment, pertubation of the normal bone reformation process and the events leading to cachexia and death. In recent years, there have been numerous in vitro studies suggesting that PSA and hK2 may play a significant biological role in these events. Also, recent data generated form reverse transcription polymerase chain reaction assays reveal that metastasis to the bone may be an early event which further underscores the need to better understand this complex and critically important process. This commentary highlights several general concepts and a few specific issues related to CaP bone metastasis with the intent of revealing numerous opportunities for further investigation and inquiry.

Animals↗

Lack of evidence of osteo-medullary metastases at diagnosis in patients with high grade gliomas.

High grade gliomas usually show a transient response to standard therapy by radiation. A local evolution leads to patient death in most of the cases. Necropsic series suggest that metastatic evolution is rather frequent in lungs, lymph nodes, bones or bone marrow. Are these metastatic deposits present initially? The authors retrospectively reviewed the bone marrow smears performed in 20 patients and the bone scans in 10 patients with high grade gliomas at time of diagnosis. None of these investigations showed metastatic deposits. It is thus suggested that metastatic deposits are probably a late event in the natural history of high grade gliomas. However, if local treatment could reach local control, metastases would probably become a major problem. Thus definitive cure of high grade glioma may require multidisciplinary approach.

Astrocytoma↗

Detection of micrometastatic prostate cancer cells in the bone marrow of patients with prostate cancer.

Thirty-five patients with prostate cancer were examined for micrometastases to the bone marrow using reverse transcription-polymerase chain reaction (RT-PCR) with primers specific for the prostate-specific antigen (PSA) gene. Of nine patients with bone metastases detectable by bone scan imaging, five patients had PSA mRNA expression in the bone marrow detectable by RT-PCR. Of 26 patients with negative bone scan findings, seven patients had PSA mRNA expression detectable in the bone marrow. RT-PCR could detect micrometastatic prostate cancer cells in the bone marrow that were not detectable by bone scan imaging. Of 16 patients with a serum PSA concentration of 25 ng ml(-1) or greater, only nine (56.3%) had bone metastases detected by bone scans. Of the remaining seven patients, five had micrometastases to the bone marrow detected by RT-PCR. Overall, 14 of 16 patients (87.5%) with a serum PSA concentration of 25 ng ml(-1) or greater had metastatic bone diseases including bone marrow micrometastases. Of 19 patients with a serum PSA concentration of less than 25 ng ml(-1), two (10.5%) had only micrometastatic disease detected by RT-PCR. A significant correlation was observed between the incidence of bone involvement and the serum PSA concentration. This study suggests that RT-PCR will potentially develop into a relevant tool to assess bone involvement including bone marrow micrometastases and establish a precise correlation between serum PSA concentration and metastatic bone disease in patients with prostate cancer.

Bone Marrow↗

Recurrent disseminated retinoblastoma in a 7-year-old girl treated successfully by high-dose chemotherapy and CD34-selected autologous peripheral blood stem cell transplantation.

A localized retinoblastoma of the left eye in a 7-year-old girl, was treated by enucleation. She received no additional therapy. Four months later, metastases of retinoblastoma in the lymph nodes, bone and bone marrow were diagnosed. Relapse chemotherapy consisting of three courses of vincristine, cyclophosphamide, etoposide and carboplatin led to a second complete remission. Subsequent high-dose chemotherapy with thiotepa, etoposide and carboplatin and autologous stem cell transplantation with CD34-selected stem cells were successful, with no adverse effects. No radiotherapy was given and the girl remains in continuous second remission with a follow-up of more than 4 years.

Antigens, CD34↗

High-dose chemotherapy and CD34-selected peripheral blood progenitor cell transplantation for patients with breast cancer metastatic to bone and/or bone marrow.

Fifty women with breast cancer metastatic to bone or bone marrow involvement on light microscopy at the time of initial evaluation were treated with high-dose chemotherapy (HDC) and peripheral blood progenitor cell (PBPC) transplantation with CD34(+) cell selection using the Isolex 300i system. All patients received induction chemotherapy. PBPC were mobilized with chemotherapy and granulocyte colony-stimulating factor. The median CD34(+) progenitor purity was 94.7% (range 72-98.7%) and recovery 38.4% (range 21-60%). Forty-eight hours after HDC with cyclophosphamide, cisplatin and carmustine, PBPC were reinfused. Median time to neutrophil count >0.5 x 10(9)/l was 9 (range 9-12) days and to platelet transfusion independence 11 (4-30) days. These data demonstrate that selected CD34(+) PBPCs allow rapid hematologic reconstitution after HDC. During follow-up, 23% of patients developed herpes zoster. Two patients developed cytomegalovirus infections. Three patients developed fungal infections. The development of these infections was not associated with steroid use but appeared more frequently in patients with diabetes mellitus. Seventy-four per cent of patients received steroids for pulmonary toxicity. Treatment-related mortality was 4%. Progression-free survival and overall survival at 35 months was 22.4% and 40.5%, with a median of 11.4 months and 15.4 months, respectively.

Adult↗

Early Reactions as Dose-Limiting Factors in Radiotherapy.

Early side effects of radiation therapy are generally the result of mitotic-linked cell death in rapidly renewing tissues and secondary impaired tissue function. Various types of acute normal tissue reactions are briefly summarized in this article. In general, with conventionally fractionated radiation treatment, the acute normal tissue reactions are within acceptable limits. However, new radiotherapy strategies, such as hyperfractionation and accelerated fractionation, induce more severe acute toxicity. Particularly, with most altered fractionation schedules, the mucosal reaction of the upper aerodigestive tract is elevated to the upper limit of tolerance. Early mucosal reactions may also become dose limiting when radiation is combined with chemotherapy as, for instance, for the treatment of head and neck cancer or pelvic neoplasms. Bone marrow is the critical organ for combination of chemotherapy and wide field irradiation. There is an increasing body of evidence that iatrogenic acute normal tissue toxicity has become a major obstacle for treatment intensification for a variety of cancers. Therefore, effective measures to ameliorate these side effects are essential for further development of cancer therapy. Methods to reduce the severity of acute toxicity are being investigated.

Journal Article↗

Microangiopathic hemolytic anemia (MAHA) as paraneoplastic syndrome in metastasized signet ring cell carcinomas: case reports and review of the literature.

We report on two spontaneous cases of microangiopathic hemolytic anemia (MAHA) as first manifestation due to metastasized signet ring carcinoma, one of gastric and one of unknown origin. The patients presented with an acute onset of Coombs negative hemolytic anemia and fragmentocytes in the peripheral blood smear which are typical for MAHA. These case reports present MAHA as a rare paraneoplastic syndrome in patients with metastasized signet ring carcinoma. Parallel to symptomatic treatment we started chemotherapy treatment (ELF and PLF regimen, respectively). In both cases we were able to control the MAHA and cancer progression.

Anemia, Hemolytic↗

[Quantitative evaluation of the suitability of magnetic resonance sequences for the detection of spinal bone marrow metastases of solid tumors].

AIM: To compare MR sequences for the examination of the bone marrow of the spine in the detection of skeletal metastases. METHODS: 20 standardised prospective studies of the cervical, thoracic or lumbar spine in patients with known skeletal metastases were evaluated quantitatively. Studies included T1w SE with and without intravenous contrast medium (CM) administration of Gd-DTPA, T2w TSE with and without frequence selective fat saturation (SPIR), opposed phase gradient echo (opGE) with and without intravenous CM administration of Gd-DTPA and T1w SE CM SPIR sequences. The quantitative parameters signal/noise ratio (SNR), contrast/noise ratio (CNR) and contrast were evaluated. RESULTS: OpGE with contrast showed the best results in SNR, CNR and C. Results were statistically significant. Good SNR and C also was found for T1w SE native. SPIR and T2w sequences were less sensitive. CONCLUSION: OpGE sequences are recommended for the detection of skeletal metastases of the spine.

Bone Marrow Neoplasms↗

[Minimal metastatic and minimal residual disease in patients with Ewing tumors].

At least 95% of Ewing tumors (ET) are characterized by an EWS-gene rearrangement with either FLI-1 or ERG and by extraordinary high MIC2/CD99 expression. Both features can be used for the specific identification of tumor cells, which might also be present in blood and bone marrow in minimal metastatic or minimal residual disease. We report the establishment of sensitive ET cell detection methods based on these characteristics. Preliminary results of 14 patients are given and two cases are reported in detail. 6/14 patients showed RT-PCR positivity in the bone marrow whereas in 8/14 patients ET cells could be detected by immunofluorescence. Only in 2 patients, one at diagnosis and one at relapse, tumor cells were detected in blood samples by RT-PCR. Peripheral blood stem cells of 5 patients showed no contamination with ET cells. The versatility of the immunocytochemical approach as compared to the RT-PCR analysis is discussed in order to explain the discrepancies between the results obtained with the two detection methods.

Adolescent↗

Diagnosis of renal cell carcinoma by bone marrow aspiration biopsy.

We report a patient who presented with persistent unclear fever, anaemia and leucopenia. A bone marrow aspiration biopsy was performed due to these symptoms, revealing malignant adenocarcinoma cells with a suspicion of renal origin. A computerized tomography confirmed the diagnosis. The patient progressed rapidly and died of widespread metastatic papillary renal cell carcinoma.

Biopsy, Needle↗

Multifocal osteosarcoma involving unusual sites.

We report a rare case of multifocal osteosarcoma (MFOS) with involvement of skeleton, lung, bone marrow, and soft tissues, presenting with paraparesis, cranial nerve palsies, subcutaneous nodules, anemia, and thrombocytopenia. MFOS with involvement of unusual sites presents problems in diagnosis and has a poor prognosis. The literature on 11 cases of MFOS with extraosseus, extrapulmonary involvement reported previously has been reviewed.

Adult↗

CD5+ extranodal marginal zone B-cell (MALT) lymphoma. A low grade neoplasm with a propensity for bone marrow involvement and relapse.

Three cases of extranodal marginal zone B-cell lymphoma (low grade B-cell lymphoma of mucosa-associated lymphoid tissue [MALT] type) in which the neoplastic B cells expressed the CD5 antigen are reported. The patients included 2 men and 1 woman, aged 44, 62, and 77 years. In all three cases, the histologic features were typical of marginal zone/MALT lymphoma, with reactive follicles, marginal zone (centrocyte-like) cells, and plasma cells. Pseudofollicles, prolymphocytes, and paraimmunoblasts were absent. In all cases, lymphoma from one or more sites expressed monotypic immunoglobulin (2 IgM kappa, 1 IgM lambda), pan B cell antigens and CD5. Two of 3 cases expressed CD43; one case expressed CD23. No case showed overexpression of the bcl-1 protein, cyclin D1. Interphase cytogenetic analysis revealed trisomy 3 in one of two cases examined. The two male patients presented with lymphoma in the ocular adnexa. One of them had marrow involvement, cervical lymphadenopathy and peripheral blood involvement at presentation; 24 months later, he developed a relapse in subcutaneous tissue. The second patient had marrow involvement 3 years later, at the time of recurrence of his orbital disease. The third patient presented with lymphoma at the base of the tongue. She subsequently developed lymphoma involving the left upper eyelid and right lacrimal sac and duct, the marrow, and the nasopharynx between 63 and 95 months after initial presentation. All of these patients presented with disease involving sites in the head and neck and all had multiple relapses or recurrences with bone marrow involvement at the time of presentation (1 case) or at relapse (2 cases). The presence of CD5 may be a marker for cases of MALT lymphoma with a tendency for persistent or recurrent disease, for dissemination to the marrow and other extranodal sites, and for leukemic involvement of the peripheral blood.

Adult↗

Generalized bone marrow metastases. High liver uptake on bone marrow immunoscintigraphy associated with extramedullary hematopoiesis.

Increased hepatic uptake and absent bone marrow uptake on bone marrow immunoscintigraphy has been reported after the formation of human antimurine antibodies. A case of generalized bone marrow metastases is presented, in whom an elevated liver uptake on bone marrow immunoscintigraphy proved to be associated with extramedullary hematopoiesis. Extramedullary hematopoiesis should be included as a possible cause of a disproportionately elevated liver uptake on bone marrow immunoscintigraphy, especially on initial studies, or on repeat studies with low human antimurine antibody titers. Tc-99m labeled BW 250/183 immunoscintigraphy may aid in the localization of suspected sites of extramedullary hematopoiesis.

Adult↗

Bone marrow suppression after strontium-89 therapy and local radiation therapy in patients with diffuse marrow involvement.

Strontium-89 is routinely used for pain control in advanced skeletal metastatic disease. A common side effect of Sr-89 therapy is a mild to moderate bone marrow suppression. To avoid complications from marrow suppression, a pretreatment platelet count of > 60,000/mm3 and a WBC count of > 2,400/mm3 are suggested. The authors present two patients who, despite satisfying these criteria, developed profound and prolonged bone marrow suppression after therapy. The severity of this response was most likely caused by pre-existing extensive bone marrow replacement with tumor. The contribution of local radiation therapy to bone marrow suppression is presumed to be minimal. The authors recommend that pretreatment criteria for determination of eligibility for Sr-89 therapy in selected patients be expanded to include steadily decreasing blood counts, and evaluation of extent of marrow involvement by biopsy or MR imaging.

Bone Marrow↗

Tc-99m MIBI localization in bone marrow: a marker of bone marrow malignancy.

To determine the potential of Tc-99m MIBI for detecting bone marrow malignancy, MIBI imaging of the femur was evaluated. There was no detectable MIBI activity in 125 of 141 (89%) control patients. Clearly demonstrated focal or tubular MIBI activity indicating intramedullary accumulation was demonstrated in 44 of 45 (98%) patients with proven marrow malignancy: 9 patients with multiple myeloma, 10 patients with malignant lymphoma, 11 patients with acute leukemia, 1 patient with chronic leukemia, and 14 patients with skeletal metastases. No abnormal MIBI activity was observed in the femur in 19 of 22 (86%) patients who had no evidence of malignant involvement in the femoral marrow, in 3 patients with solitary plasmacytomas of the spine, sternum or iliac bone, or in 16 patients with malignant lymphoma. In 12 of 24 patients with acute leukemia in complete remission, no abnormal MIBI accumulation was shown in the femur, but in 12 patients, abnormal accumulation indicating residual leukemic activity was demonstrated. MIBI imaging correlated extremely well with MRI studies; 26 of 28 patients with focal or tubular increased MIBI activity in the femur showed decreased signal on T1-weighted images and a high signal on short inversion recovery images, and 11 patients with no abnormal activity showed a high signal on T1 images. MIBI imaging of the femoral bone marrow may be a new modality for detecting marrow malignancy.

Adult↗