Diagnosis Of Bone Marrow Metastasis Research Articles

Bone marrow metastasis in nonhematological malignancies: A study from tertiary care center.

Metastatic cancer presents a treatment challenge to clinicians, particularly for patients with bone marrow infiltration. For tumor staging, therapy selection, and prognosis risk stratification, the status of the bone marrow should be known for the presence or absence of metastasis. The study aimed to evaluate the hematological findings and comprehensive analysis of bone marrow in cases of nonhematological malignancies with bone marrow metastasis. This retrospective study comprised a record retrieval of the departmental archives for the past 6 years. A total of 331 patients with nonhematological malignancies were found, of whom 31.42% (104/331) showed bone marrow metastasis. An integrated clinical approach with bone marrow examination findings and immunohistochemistry whenever necessary was used to achieve a definitive diagnosis of bone marrow metastasis. Among the study population, 31.42% (104/331) of patients had nonhematological malignancies that metastasized to the bone marrow. Most of the patients with bone marrow metastasis had anemia, which was found in 77.88% (81/104) of the cases. Leukoerythroblastic reaction was noted in 31.73% (33/104) of the cases, and thrombocytopenia was found in 25% (26/104) of the cases. The most common malignancy with bone marrow metastasis in adults was prostatic adenocarcinoma (28.1%) (9/32) and in pediatric cases, neuroblastoma (53.9%) (52/98). It is essential to diagnose nonhematological malignancies that have metastasized to the bone marrow since this necessitates tumor staging, therapy selection, and prognosis risk stratification. To conclude, not a single hematological parameter is predictive of bone marrow metastasis; however, unexplained anemia, a leukoerythroblastic blood picture, and thrombocytopenia in peripheral blood should raise suspicion for bone marrow metastasis in cases of nonhematological malignancies.

An unexpected finding of bone marrow metastasis from adenocarcinoma of lower gastrointestinal tract origin: Case report

Bone marrow examination is an essential tool for diagnosis of many diseases including both hematological and non hematological tumors. Bone marrow is commonly involved by many metastatic solid tumors. Bone marrow aspirates, and biopsies have been found to be more useful than radiological investigations in early diagnosis of bone marrow metastasis.Here we present a case of a 75 years old male patient presenting with acute sudden onset chest pain along with multiple lytic sclerotic foci in lumbar vertebrae, bilateral ribs, clavicle, scapula and sternum along with fractures in multiple ribs. CBC findings showed anemia with thrombocytopenia. Bone marrow examination revealed an infiltration of a metastatic tumor in bone marrow which was further confirmed to be of lower gastrointestinal tract in origin on IHC findings.A high suspicion for bone marrow metastasis should be considered in cases who present primarily with abnormalities in peripheral blood count and a vigilant search for metastatic cells on aspirate smears and imprint smears can help in early diagnosis of bone marrow metastasis by solid tumors.

FDG-PET/CT Demonstrates Splenic Angiosarcoma Bone Marrow Metastasis.

Some patients with splenic angiosarcoma initially manifest thrombocytopenia owing to hypersplenism or tumor-related bone marrow fibrosis. The diagnosis of bone marrow metastasis in patients with splenic angiosarcoma is challenging, as the presentation mimics idiopathic thrombocytopenic purpura or primary myelofibrosis. Our case showed diffuse FDG uptake in the vertebral bodies, sacroiliac bone, humerus, femur, and clavicles. It was pathologically diagnosed as bone marrow metastasis of splenic angiosarcoma. We believe that the heterogeneous FDG accumulation in the bone marrow, although nonspecific, can be useful for the diagnosis of the bone marrow metastasis in patients with splenic angiosarcoma.

Clinical features and treatment of patients with lung adenocarcinoma with bone marrow metastasis.

Bone marrow metastasis occurs in lung adenocarcinoma patients with a poor prognosis due to the late course and lack of definitive treatments, although reports on this are limited. This study analyzed the clinical manifestation, laboratory examination, treatment, and prognosis of patients with lung adenocarcinoma with bone marrow metastasis. All patients were confirmed to have bone marrow infiltration by bone marrow aspiration. The clinical data of 12 patients with lung adenocarcinoma with bone marrow metastasis were analyzed retrospectively. The prognostic factors were analyzed by Kaplan-Meier statistics. The common biomarker abnormalities in 12 patients were elevated carcinoembryonic antigen in 12 cases (100%), elevated lactate dehydrogenase in 9 cases (75%), increased alkaline phosphatase and anemia in 8 cases each (66.7%), and thrombocytopenia in 4 cases (33.3%). After diagnosis of bone marrow metastasis, 5 patients were treated with platinum-based chemotherapy, 3 patients received chemotherapy and targeted drug tyrosine kinase inhibitor (TKI) therapy, 2 patients received simple TKI therapy, and 2 patients received only best supportive care (BSC) therapy. The median duration of survival after the diagnosis of bone marrow involvement was 422 days. The survival time of patients receiving TKI therapy after bone marrow metastasis was significantly better than that of patients receiving only BSC and chemotherapy (χ2=4.636, P=0.031). The survival period of patients with lung adenocarcinoma with bone marrow metastasis is short, and targeted drug TKI treatment can prolong the survival time for patients with EGFR mutation-carrying lung adenocarcinoma with bone marrow metastasis.

Abstract P1-18-05: Management of bone marrow involvement in advanced breast cancer: Retrospective multicenter cohort study

Abstract Background: Optimal management of bone marrow metastasis (BMM) in advanced breast cancer (ABC) remains unknown. Associated severe cytopenias often urge treatment, but they are also a challenging factor for delivering chemotherapy (CT). Since BMM in ABC is infrequent, available data are scarce. Aim: Clinical and prognostic characterization of ABC patients with BMM and its management; evaluation of the effectiveness of treating BMM with more myelosuppressive CT regimen (that we hypothesized that could be more active in the BMM) Vs. less myelosuppressive regimen. Methods: Retrospective cohort study of patients with pathological confirmation of BMM (positive myelogram or osteomedullary biopsy) between Jan'2010 and Dec'2016 in the two major Portuguese cancer centers. Patients with diagnosis of a second carcinoma or active hemato-oncological condition within 5 years before BMM were excluded. We considered the more myelosuppressive regimens those with > 5% risk of febrile neutropenia according to Truong et al 2015(1). Kaplan-Meier and log-rank methodology were used to estimate survival and Cox regression to identify the covariates with independent prognostic value. Statistical level of significance was 5%. Results: We included 74 patients: 74% with disease stage I-III at presentation, 74% ductal and 12% lobular invasive carcinomas, 58% grade 2 and 27% grade 3, 80% hormone receptor + / HER2-, 4% HER2+ and 12% triple negative (TN). Median time from ABC diagnosis to BMM was 10 months (IQR 2-36), synchronous in 34%. At diagnosis of BMM, median age was 57 years-old (IQR 47-65), 57% were post-menopausal, 97% had bone metastasis, 50% had visceral metastasis, 53% performed ≥ 2 previous palliative systemic treatments and 53% were exposed to bisphosphonates. The most frequent immunohistochemistry change in BMM biopsy was the loss of progesterone receptor expression (37%). Bicytopenia (anemia/thrombocytopenia) was the trigger for BMM investigation in 69% of cases, with grade 3-4 anemia in 16% and grade 3-4 thrombocytopenia in 26%. Median survival after BMM diagnosis was 5 months (95% CI, 3-11); overall survival at 12 and 24 months were 35% (CI 26-48%) and 24% (CI 15-36%), respectively. First treatment after BMM was CT in 58% (median survival, 11 months) and endocrine therapy in 14% (median survival, 3 months). An anti-HER2 regimen was used in 4% and 22% did not receive any treatment after BMM. On multivariate analysis, TN subtype (HR 4.02, CI 1.46-11.01), thrombocytopenia (G0 reference; G1-2: HR 2.47, CI 1.11-5.56; G3-4: HR 4.89, CI 1.85-12.91) and ≥ 2 palliative systemic treatments (HR 2.77, CI 1.46-5.27) were associated with worse prognosis. Within those treated with CT, there was a trend for a deleterious survival effect of more myelosuppressive regimens (HR 2.19, CI 0.94-5.09; 5 months Vs. 14 months, n=31), after controlling for subtype, number of previous regimens and thrombocytopenia. Conclusion: BMM was not a late event in ABC disease course and had worse prognosis in multi-treated patients, in TN subtype and in the presence of thrombocytopenia. No benefit was shown with the use of more myelosuppressive CT regimens. (1)Truong J et al, Ann Oncol. 2016 Apr;27(4):608-18. Citation Format: Martins-Branco D, Ferreira SC, Pereira I, André S, Varelas A, Leal C, Esteves S, Abreu MH, Sousa S, Moreira A, Brito M. Management of bone marrow involvement in advanced breast cancer: Retrospective multicenter cohort study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-18-05.

Clinical Analysis of Small Cell Lung Cancer with Bone Marrow Metastases

背景与目的小细胞肺癌（small cell lung cancer, SCLC）恶性程度高，早期易发生骨髓转移，但其相关报道有限。本研究分析SCLC骨髓转移患者的临床表现，实验室检查、治疗以及预后。方法回顾性分析26例SCLC骨髓转移患者的临床资料，分析其预后相关因素。结果26例SCLC骨髓转移患者的中位年龄57岁，从诊断SCLC到确诊骨髓转移的中位时间为8天。多数患者（96.2%）同时伴有其他脏器转移。最常见的实验室异常为乳酸脱氢酶增高19例（73.1%），血小板减少和碱性磷酸酶增高各11例（42.3%），贫血7例（26.9%）。全组在诊断骨髓转移后，6例未化疗，20例化疗，其中16例至少接受了2个周期化疗。全组患者确诊骨髓转移后的中位生存期为15.7周（0.1周-82.9周），接受化疗患者的生存期显著优于未化疗者（χ2=33.768, P < 0.001）。多因素分析显示未化疗是独立的预后不良的因素（P < 0.05）。结论SCLC骨髓转移患者的生存期短，化疗可延长患者的生存。

Predictive Value of Clinical and Laboratory Parameters for Overt Bone Marrow Metastasis in Patients with Solid Malignancy

Bone marrow (BM) metastases are known to worsen the outcome in patients with malignancies and alter the choice of the treatment regimen. In an attempt to identify routine parameters for the prediction of BM metastasis we evaluated the clinical and laboratory data of 103 patients with metastatic solid tumors. We also assessed which of these factors appeared to influence survival. Three laboratory abnormalities were found to be predictive of metastasis on BM biopsy: thrombocytopenia < 50 × 109/L OR 14.4; p = 0.02; hypocellular or dry tap aspirate OR 7.0; p = 0.02 and high serum alkaline phosphatase OR 6.5; p = 0.03. Three additional factors were found to be associated with deceased survival. Thrombocytopenia was associated with decreased survival from a median of 0.8 months to 4.1 months, p < 0.0001. Serum LDH levels more than twice the upper limit of normal were also reduced survival from 1.8 months versus 4.7 months, p = 0.03. Finally, the initial diagnosis of malignancy by bone marrow examination was associated with reduced survival from 1.8 months vs. 4.0 months, p = 0.03 in individuals where BM metastases were not the presenting feature of malignancies. Use of these simple clinical parameters may help in the early diagnosis of bone marrow metastases and improve clinical approach.

Metastatic Bone Marrow Tumors Manifested by Hematologic Disorders: Study of Thirty-Four Cases and Review of Literature

Purpose: Bone marrow metastasis of cancer is a sign of extensively hematogenous spreading of cancer and may be a terminal event of those patients. With the improvement of systemic chemotherapy for malignant disease, some patients may have longer survival. We plan to find out the clinical hematologic presentation and prognostic factors in cancer patients with bone marrow metastasis. Materials &amp; Methods: In this retrospective study, we reviewed the results of 162 bone marrow examination carried out in adult malignancy patients (colon, lung, gastric, breast and prostate cancers) between January 2002 and December 2012 in Changhua Christian Hospital. The indication for bone marrow study for those patients with hematologic disorders included: leukoerythroblastosis, microangiopathic hemolytic anemia, unknown etiology of anemia, thrombocytopenia, bicytopenia and pancytopenia. Statistics analysis used SPSS 18.0 and overall survival was analyzed with the use of Kaplan-Meier curves and the log-rank test. Results: Thirty-four patients (20.9%) had evidence of involvement of the bone marrow by a solid tumor, most common cancers were prostate and lung. At the time of diagnosis, the most common hematologic disorders were leukoerythroblastosis and microangiopathic hemolytic anemia. Median survival after the diagnosis of bone marrow metastasis with supportive care only compared with definite treatments was 0.3 months and 20.6 months (p&lt;0.0001). Patients with visceral organ metastasis (0.4 months vs 6.4 months, respectively; p &lt;0.002) and anemia (2.1 months vs 6.4 months, p=0.031) had inferior survival. Patents without any cytopenia had better survival (12.5 months vs 4.1 months, p=0.029). Initial level of thrombocyte and neutrophil, bone marrow infiltration type (focal or diffuse) and disease status were not significant prognostic factor. Conclusions: Visceral metastasis and anemia are most poor prognostic factors in solid cancers with bone marrow metastasis. Since the improvement of the diagnosis and treatment for cancers during the recent decades, a portion of patients can be had better disease control after definite treatment especially in breast and prostate cancers with bone marrow metastasis.

Clinical profile and outcome of patients with breast cancer and bone marrow metastasis (BMM) at the Brazilian National Cancer Institute (INCA).

e11515 Background: Breast cancer (BC) is the second most common cancer in the world. Advanced disease is associated with worse prognosis, especially when visceral metastasis are diagnosed. The objective of this study is to evaluate the clinical characteristics and outcome of pts with BC and BMM. Methods: Retrospective chart review of clinical data from pts with BC and histopathological confirmation of BMM treated at the Brazilian National Cancer Institute between 1996 and 2008. Results: Clinical data was available from 88 consecutive pts. All pts had cytopenias, and this was the clinical indication for the BM biopsy. Median age at diagnosis of BC was 53y (33-72); median interval between BC and BMM diagnosis was 35 months (0-85). Infiltrating ductal carcinoma represented 84.4% of cases, infiltrating lobular carcinoma 8.8%, mucinous carcinoma 5.5%, and mixed tumor histology 1%; histological grade I 3.3%, 22.2% in II and III in 15.5% (59% not rated); hormone receptor was positive in 64.4%, negative in 23.3%; stage at diagnosis: 35.5% stage IV, 32.2% IIIB, 36.6% IIIA, 5.5% IIB, 4.4% II. When BMM was diagnosed, 90% had bone metastasis, 36.6% had liver metastasis, 26.6% skin, 10% pleural/lung, 10% central nervous system. Most pts received treatment after the diagnosis of BMM: 31% chemotherapy, 8.8% endocrine therapy, 18.8% chemo and endocrine therapy. Median overall survival after the BMM diagnosis: 16 weeks (0-480). Conclusions: BMM was associated with advanced disease and poor overall survival. No significant financial relationships to disclose.

Platelet size has diagnostic predictive value for bone marrow metastasis in patients with solid tumors

Though not very common, solid tumor involvement of the bone marrow (BM) may have serious consequences. Recent studies have shown that mean platelet volume (MPV) is a good indicator for BM disease in the differential diagnosis of thrombocytopenia. We investigated the significance of MPV in the diagnosis of BM metastasis in patients with solid tumors. Patients with histologically-verified solid tumors for whom BM biopsy specimens were available (n = 121) and healthy controls (n = 62) were included in this retrospective study. A total of 183 individuals were analyzed. Of the patients, 61 had a diagnosis of BM metastasis (Group A), 60 did not have BM metastasis (Group B). Group B and C (healthy controls) constituted the control group without BM metastasis (n = 122). The mean MPV was 7.0 +/- 0.8 fl in patients with BM metastasis and 8.4 fl in the control group (P < 0.001). A cut-off point of <7.4 fl was found to have significant predictive value according to receiver-operating characteristics curve analysis. This cut-off point had 85% positive predictive value and 90% negative predictive value in the diagnosis of BM metastasis (odds ratio: 53; 95% confidence interval: 20-135), and a sensitivity of 82.7% and specificity of 89.6%. MPV can be used as a reliable marker to guide the clinician as to the likely presence or absence of BM metastasis in patients with solid tumors.

Diagnosis of Bone Marrow Metastases in Children with Solid Tumors and Lymphomas: Aspiration, or Unilateral or Bilateral Biopsy?

Background Malignancies are among the most common causes of death in children. The present study was undertaken to evaluate and compare bone marrow aspiration and unilateral biopsy to detect bone marrow metastases in pediatric patients, using bilateral biopsy as the gold standard. Methods During a 6-month period, 63 consecutive newly diagnosed children with confirmed malignant diseases other than leukemia were evaluated for bone marrow metastases or infiltration. Biopsies were obtained from both right and left posterior iliac crests whereas aspiration was performed only at the right crest. Interpretation to the right-side biopsy was considered as the unilateral biopsy result, whereas the bilateral biopsy result was as follows: positively was accepted if one or both of the two-side samples were qualified as positive, while a negative result was considered only if both sides were negative. The bilateral biopsy was considered the gold standard, and sensitivity, specificity, positive and negative predictive value, and false positive and negative rates were computed for the unilateral biopsy and aspiration procedure. Results We identified bone marrow metastases in 11 (17.5%) patients. The sensitivity was the only significant difference ( p <0.05) observed between unilateral biopsy and aspiration. Finally, of the 63 patients, unilateral biopsy was reported as inadequate in one patient (1.6%), while aspiration was inadequate in two (3.2%). Conclusions Unilateral biopsy was better than bone marrow aspiration. However, because bilateral biopsy is the gold standard, we recommend using this and bone marrow aspiration simultaneously to evaluate a pediatric patient with any malignancy potentially infiltrating bone marrow.

Efficient confidence bounds for ROC curves.

The specificity and sensitivity of a quantitative diagnostic marker depends on the selected cut-off point. The ROC curve is generated by plotting sensitivity against specificity as the cut-off point runs through the whole range of possible marker values. Confidence bounds for ROC curves may be constructed by combining two separate confidence intervals for sensitivity and specificity. In the present paper, a more efficient method, which is based on a statistical test introduced by Greenhouse and Mantel, is presented. The resulting 95 per cent confidence intervals are up to 40 per cent smaller. A formula is given to calculate the sample size necessary to obtain a confidence interval of a stipulated length at a specified point of the ROC curve. As an example, the performance of a tumour marker in the diagnosis of bone marrow metastases is investigated.

Detection of tyrosine hydroxylase mRNA and minimal neuroblastoma cells by the reverse transcription-polymerase chain reaction

To facilitate the diagnosis of bone marrow metastasis in neuroblastoma, we have developed a method of amplifying and detecting the tyrosine hydroxylase (TH) mRNA sequence in bone marrow cells using a combination of reverse transcription and the polymerase chain reaction (RT/PCR). By this method, the sequence of TH was detected clearly in the neuroblastoma tissues of all 6 patients and not detected in the bone marrow cells of any of the 9 negative control children. In a reconstitution experiment, 1 neuroblastoma cell per 100 000 normal bone marrow cells could be detected, thus indicating the great sensitivity of this method. Based on these results, this technique may be of value in the diagnosis and treatment follow-up of bone marrow metastasis of neuroblastoma.

Nasopharyngeal Carcinoma with Bone Marrow Metastasis

Five of 23 patients with recurrent nasopharyngeal carcinoma (NPC) were diagnosed to have bone marrow metastasis. They all had advanced local-regional disease, and were treated with neoadjuvant chemotherapy and definitive radiotherapy after the initial diagnosis. Bone marrow metastasis developed 4-24 months later. The clinical features were anemia (5 of 5), leukopenia (3 of 5), thrombocytopenia (4 of 5), sepsis (3 of 5), tenderness of the sternum (3 of 5), and fever (4 of 5). Patients frequently had elevation of serum lactic dehydrogenase (LDH), alkaline phosphatase (ALK-P), and IgG and IgA antibody titers to Epstein-Barr viral capsid antigen when bone marrow involvement was diagnosed. However, clinical manifestations and laboratory tests were not specific. It is important that three patients had normal bone scans. All five patients had a rapid downhill course; four patients died within 23 days, and the fifth 3 months after the diagnosis of bone marrow metastasis. We concluded that bone marrow was a common metastatic site in NPC patients. Bone marrow metastasis adversely affected patients' survival and required a high index of suspicion for diagnosis. We suggested that bone marrow biopsy should be considered as a routine staging procedure in NPC patients and indicated especially when patients presented with abnormal blood counts, sepsis, bone pain, or tenderness of the sternum. It may be positive in the face of a normal bone scan.