BACKGROUND: Small cell lung cancer (SCLC) is highly malignant and prone to bone marrow metastasis in early stage, but its related reports are limited. This study analyzed the clinical feature, laboratory examination, treatment and prognosis of SCLC patients with bone marrow metastasis. METHODS: The clinical data of 26 SCLC patients with bone marrow metastasis were analyzed retrospectively. Prognostic factors were evaluated. RESULTS: The median age of 26 patients was 57 years and the median time from diagnosis of SCLC to confirmed bone marrow metastases was 8 d. Most patients (96.2%) were accompanied by other organ metastases. The most common laboratory abnormalities were elevated lactate dehydrogenase in 19 cases (73.1%), thrombocytopenia and elevated alkaline phosphatase respectively in 11 cases (42.3%) and anemia in 7 cases (26.9%). Twenty patients had received chemotherapy and the remaining 6 patients had not. Of this group, 16 patients received at least 2 cycles of chemotherapy after the diagnosis of bone marrow metastasis. The median survival time was 15.7 wk (0.1 wk-82.9 wk) after diagnosis of bone marrow metastasis. The survival of patients with chemotherapy was significantly better than that of those without chemotherapy (χ²=33.768, P<0.001). Multivariate analysis showed that no chemotherapy was independent poor prognostic factors (P<0.05). CONCLUSIONS The SCLC patients with bone marrow metastasis have short survival, whereas chemotherapy can extend the survival of patients.
Aged ; Bone Marrow ; pathology ; Bone Marrow Neoplasms ; mortality ; pathology ; secondary ; Female ; Humans ; Lung Neoplasms ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Retrospective Studies ; Small Cell Lung Carcinoma ; pathology

OBJECTIVETo explore the formation of pre-metastatic niche in the mouse lung and to study the underlying molecular mechanisms whereby primary breast carcinoma-derived factors mediate recruitment of bone marrow-derived cells (BMDCs) and affect the formation of pre-metastatic lung environment before the arrival of tumor cells.

METHODSMammary carcinoma 4T1 cells were inoculated into the mammary gland to construct mouse model of breast cancer. Confocal microscopy was used to detect the recruitment of BMDCs in the pre-metastatic lungs. The expression of factors in the mouse sera and 4T1 cell culture media was assayed using RayBio Custom mouse cytokine antibody array kit. The mice were injected daily with recombinant VEGF for 7 consecutive days to observe the effect of VEGF on BMDCs recruitment in the mouse lung.

RESULTSNo BMDCs were observed in the lungs of control and 4T1-tumor-bearing mice on day 0. On day 7 and 14, clusters of BMDCs observed in the lungs of 4T1-tumor-bearing mice were 8.7±2.2/objective field and 48.8±3.2/objective field, respectively, significantly higher than those in the control mice (1.1±0.8/objective field and 3.1±1.7/objective field) (P<0.05 for both). Confocal microscopic observation found that metastatic breast cancer cells preferentially facilitate BMDCs recruitment sites in the pre-metastatic mouse lungs. The levels of VEGF, GM-CSF, and IL-6 in the serum of 4T1-tumor-bearing mice were significantly increased compared with those in the control group (P<0.05 for all). However, VEGF was detected only in the culture media of 4T1 cells. The amount of BMDCs in the mouse lung tissue was (22.8±3.6)/objective field in the VEGF group and (3.1±0.4)/objective field in the control group (P<0.05). There were 36.8±5.4 metastatic foci in the lung tissue of VEGF group and 12.6±2.2 in the control group (P<0.05).

CONCLUSIONSThe results of this study demonstrate that primary breast cancer cells can alter the lung microenvironment during the pre-metastatic phase and induce the formation of pre-metastatic niche. Primary tumor cell-derived VEGF may be a crucial factor responsible for the formation of pre-metastatic niche.

Animals ; Bone Marrow Cells ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Disease Models, Animal ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor ; blood ; Humans ; Interleukin-6 ; blood ; Lung ; pathology ; Lung Neoplasms ; secondary ; Mice ; Recombinant Proteins ; administration & dosage ; Time Factors ; Tumor Microenvironment ; Vascular Endothelial Growth Factor A ; administration & dosage ; physiology ; secretion

The records of 63 high-risk neuroblastoma patients with bone marrow (BM) tumors at diagnosis were retrospectively reviewed. All patients received nine cycles of induction chemotherapy followed by tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT). Follow-up BM examination was performed every three cycles during induction chemotherapy and every three months for one year after the second HDCT/auto-SCT. BM tumor cells persisted in 48.4%, 37.7%, 23.3%, and 20.4% of patients after three, six, and nine cycles of induction chemotherapy and three months after the second HDCT/auto-SCT, respectively. There was no difference in progression-free survival (PFS) rate between patients with persistent BM tumor and those without during the induction treatment. However, after tandem HDCT/auto-SCT, the PFS rate was worse in patients with persistent BM tumor than in those without (probability of 5-yr PFS 14.7% +/- 13.4% vs. 64.2% +/- 8.3%, P = 0.009). Persistent BM tumor during induction treatment is not associated with a worse prognosis when intensive tandem HDCT/auto-SCT is given as consolidation treatment. However, persistent BM tumor after tandem HDCT/auto-SCT is associated with a worse prognosis. Therefore, further treatment might be needed in patients with persistent BM tumor after tandem HDCT/auto-SCT.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Bone Marrow Neoplasms/pathology/*secondary/*therapy ; Child ; Child, Preschool ; Combined Modality Therapy/methods ; Female ; Humans ; Induction Chemotherapy/methods ; Infant ; Infant, Newborn ; Male ; Neoplasms, Multiple Primary/pathology/*therapy ; Neuroblastoma/*pathology/*therapy ; Prognosis ; Retrospective Studies ; Risk Factors ; Stem Cell Transplantation/*methods ; Treatment Outcome ; Young Adult

Adolescent ; Bone Marrow Neoplasms ; secondary ; Humans ; Male ; Prostatic Neoplasms ; pathology ; Sarcoma ; pathology

OBJECTIVETo analyze the clinical manifestations and hematologic parameters and observe the cytomorphological features of metastatic tumors in the bone marrow originating from different primary sites.

METHODSThe clinical data of 77 patients with bone marrow metasta tumors admitted between 2009 and 2014 between 2009 and 2014 in General Hospital of PLA were studied retrospectively to analyze the indications of laboratory examinations (hematological laboratory tests, tumor markers, peripheral blood films, and bone marrow aspirates).

RESULTSOf the 77 patients analyzed, 64.9% were over 50 years of age. The most common clinical characteristics were bone pain (65%), anemia with thrombocytopenia (63.6%) and leukoerythroblastic reaction (61%). The hematological abnormalities included elevation of ESR, ALP, LDH, tumor markers, and hypoproteinemia. Cytological examination of bone marrow aspiration samples revealed different morphological characteristics of the metastatic cells from different primary sites; in most of the cases, scattered or clustered metastatic cells and degenerative tumor cells were found on the edge of the bone marrow smears.

CONCLUSIONDetection of the primary tumor site is difficult by cytological examination of bone marrow aspiration samples, but the cytological findings can be of value in the diagnosis of neuroblastoma, small cell lung cancer and gastric cancer (signet ring cell carcinoma). A definite diagnosis of bone marrow metastatic tumor relies on a combined evaluation of the disease history, clinical symptoms and laboratory findings.

Anemia ; Biomarkers, Tumor ; blood ; Bone Marrow ; pathology ; Bone Marrow Examination ; Bone Marrow Neoplasms ; secondary ; Carcinoma ; pathology ; Hematologic Tests ; Humans ; Neuroblastoma ; Retrospective Studies ; Small Cell Lung Carcinoma ; Stomach Neoplasms ; Thrombocytopenia

BACKGROUND: The prognostic impact of the presence of differentiating neuroblasts in bone marrow (BM) remains unclear in BM metastatic neuroblastoma (NB). We aimed to identify the prognostic impact of differentiating neuroblasts in BM at diagnosis and after chemotherapy. METHODS: A total of 51 patients diagnosed with BM metastatic NB at Asan Medical Center between January 1990 and July 2005 were enrolled. BM histology and laboratory data along with overall survival (OS) were compared with regard to the differentiation status of neuroblasts in BM at diagnosis and after chemotherapy. RESULTS: Among the 51 patients, 13 (25.5%) exhibited differentiating neuroblasts in BM at diagnosis and 17/51 (33.3%) exhibited them after chemotherapy. The only significant difference among patient groups was the improved OS in patients with differentiated neuroblasts in BM at diagnosis (P=0.021). In contrast, the differentiation status of neuroblasts in BM after chemotherapy did not affect OS (P=0.852). CONCLUSIONS: Our study is the first report describing the presence of differentiating neuroblasts in BM. The presence of differentiating neuroblasts in BM at diagnosis may be a favorable prognostic factor for patients with BM metastatic NB; however, the same phenomenon after chemotherapy is irrelevant to prognosis.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bone Marrow/*pathology ; Bone Marrow Cells/*cytology ; Bone Marrow Neoplasms/*diagnosis/secondary ; Cell Differentiation ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Karyotyping ; Male ; Neoplasm Grading ; Neuroblastoma/*diagnosis/drug therapy/pathology ; Prognosis ; Survival Analysis ; Young Adult

This study was aimed to explore the value of one-step method of bone marrow aspiration and biopsy applied in diagnosis of the bone marrow metastatic cancer. The total of 46 cases of bone marrow metastatic cancer were analyzed retrospectively, and the results of the bone marrow smear and the bone marrow biopsies were compared. The results indicated that the success rate of one-step method of bone marrow aspiration and biopsy was 95.7%. Metastatic carcinoma cells in clumps or clusters with morphological changes were observed in the bone marrow biopsies of the 45 patients (97.8%), but the metastatic carcinoma cell clusters were observed only in bone marrow smears of the 25 patients (54.3%). There were mild to moderate hyperplasia of fibrous tissue in the patients with metastatic cancer. In addition to the 83.3% diagnostic rate of esophageal cancer, the rest diagnostic rate of bone marrow biopsy for metastatic carcinoma was 100%. The diagnostic rate of bone marrow smear for ovarian cancer, lung cancer, gastric cancer, thoracic tumor, sigmoid colon cancer, esophageal cancer and metastatic cancer of unknown primary cancers were 33.3%, 50%, 72.2%, 60%, 50%, 33.3% and 25%, respectively. The diagnostic rate of bone marrow biopsy was higher than that of bone marrow smear. It is concluded that the success rate of drawing specimen by one-step method of bone marrow aspiration and biopsy is high. The bone marrow biopsy is better than that of aspiration in diagnosis of metastatic cancer. Combining biopsy with aspiration can improve the accuracy of diagnosis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biopsy ; methods ; Bone Marrow ; pathology ; Bone Marrow Examination ; methods ; Bone Marrow Neoplasms ; diagnosis ; pathology ; secondary ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; diagnosis ; Retrospective Studies ; Young Adult

Metastasis represents by far the most feared complication of prostate carcinoma and is the main cause of death for patients. The skeleton is frequently targeted by disseminated cancer cells and represents the sole site of spread in more than 80% of prostate cancer cases. Compatibility between select malignant phenotypes and the microenvironment of colonized tissues is broadly recognized as the culprit for the organ-tropism of cancer cells. Here, we review our recent studies showing that the expression of platelet-derived growth factor receptor alpha (PDGFRα) supports the survival and growth of prostate cancer cells in the skeleton and that the soluble fraction of bone marrow activates PDGFRα in a ligand-independent fashion. Finally, we offer pre-clinical evidence that this receptor is a viable target for therapy.
Animals ; Antibodies, Monoclonal ; therapeutic use ; Bone Marrow ; enzymology ; pathology ; Bone Neoplasms ; prevention & control ; secondary ; Enzyme Activation ; Humans ; Male ; Prostatic Neoplasms ; drug therapy ; enzymology ; pathology ; Receptor, Platelet-Derived Growth Factor alpha ; antagonists & inhibitors ; genetics ; immunology ; metabolism ; Signal Transduction ; Transcriptional Activation

Adult ; Bone Marrow Transplantation ; Humans ; Male ; Pancreas ; pathology ; Pancreatic Neoplasms ; diagnosis ; secondary ; surgery ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; complications ; diagnosis ; physiopathology

OBJECTIVETo explore the diagnostic value of bone marrow biopsy for bone marrow metastatic tumor with unknown primary tumor site.

METHODSThirty-eight cases of metastatic bone marrow tumors were diagnosed by light microscopy, and the bone marrow samples from these cases with unknown primary tumor sites were examined by immunohistochemistry.

RESULTSIn all the cases, the bone marrow was infiltrated by tumor cells between the bone trabecula. Twenty patients were identified to have poorly differentiated adenocarcinomas, 6 had mucinous adenocarcinomas, 6 had mucinous carcinomas, 4 had poorly differentiated squamous cell carcinomas, and 2 had melanoma. Immunohistochemistry identified the primary tumor sites in these cases, including 12 stomach cancers, 10 breast cancers, 8 prostate cancers, 4 lung cancers, 1 dorsal melanoma, 1 left foot melanoma, and 2 nasopharyngeal cancers.

CONCLUSIONProper immunohistochemistry can help determine the primary tumor sites in patients with metastatic bone marrow tumor with unknown primary tumor sites.

Adenocarcinoma ; diagnosis ; pathology ; secondary ; Adult ; Aged ; Biopsy, Needle ; Bone Marrow Examination ; methods ; Bone Marrow Neoplasms ; diagnosis ; pathology ; secondary ; Female ; Humans ; Lung Neoplasms ; diagnosis ; pathology ; Male ; Middle Aged ; Neoplasms, Unknown Primary ; diagnosis ; Stomach Neoplasms ; diagnosis ; pathology