| Abstract|| |
Background: Bone marrow biopsy is widely used method for diagnosis, follow-up and staging of hemato-oncologic diseases. This procedure is also used for determining the bone marrow metastasis in patients with solid tumors. In this study, clinical, hematological, and pathological features of 58 patients with bone marrow metastases diagnosed by bone marrow biopsies were examined retrospectively Materials and Methods: Among 3345 bone marrow biopsies performed in our hospital between January 2006 and August 2013, 58 cases with solid tumor metastasized to bone marrow were included in this study. Results: Among 58 cases with solid organ carcinoma metastasis in bone marrow, mean age was 59.9. Thirty-nine cases were found to have a known primary tumor focus. The most common tumors metastasized to bone marrow were breast carcinomas (23 patients, 59%), gastric carcinomas (6 patients, 15.3%), prostate carcinomas (4 patients, 10,2%), and lung carcinomas (3 patients, 7.7%), respectively. Nineteen patients were firstly diagnosed from bone marrow biopsies as metastatic carcinomas. The median overall survival after bone marrow metastasis was 28 days (95% confidence interval: 7.5-48.4). The median overall survival difference was not statistically significant between patients with primary known and unknown tumor (P = 0.973). Statistically significant difference was observed between the survival of breast cancer and gastric cancer (P = 0.028). The most common hematologic symptom was the coexistence of anemia and thrombocytopenia (31%), thrombocytopenia (27.6%) and anemia (20.7%) alone. The median overall survival difference was statistically significant between patients who have anemia and thrombocytopenia (P < 0.005). Conclusion: Bone marrow biopsy is an easily accessible, easily applied, a useful procedure for diagnosing metastatic diseases in patients with hematologic symptoms such as anemia and thrombocytopenia besides being an uncomfortable procedure for patients. Furthermore, it is useful in predicting the prognosis and short survey after diagnosing bone marrow metastasis.
Keywords: Anemia, bone marrow, neoplasm metastasis, thrombocytopenia
|How to cite this article:|
Kucukzeybek BB, Calli AO, Kucukzeybek Y, Bener S, Dere Y, Dirican A, Payzin KB, Ozdemirkiran F, Tarhan MO. The prognostic significance of bone marrow metastases: Evaluation of 58 cases. Indian J Pathol Microbiol 2014;57:396-9
|How to cite this URL:|
Kucukzeybek BB, Calli AO, Kucukzeybek Y, Bener S, Dere Y, Dirican A, Payzin KB, Ozdemirkiran F, Tarhan MO. The prognostic significance of bone marrow metastases: Evaluation of 58 cases. Indian J Pathol Microbiol [serial online] 2014 [cited 2018 Nov 17];57:396-9. Available from: http://www.ijpmonline.org/text.asp?2014/57/3/396/138728
| Introduction|| |
Bone marrow biopsy is a used technique either in diagnosis, staging and follow-up of hematological diseases or staging and determining bone marrow metastasis of solid tumors. Diagnosis of bone marrow metastasis is extremely important because of the effect on selecting treatment methods and survey in patients with solid tumors.  Bone marrow is a target of hematogenic spread of solid tumors as well as other solid organs.  In 1935, Reich reported as bone marrow aspirates from sternum may contain tumor cells, which was later proved by many researchers. , Bone marrow aspirates, and biopsies were found to be more useful than radiological methods and bone scintigraphy in the diagnosis of metastatic tumors by 1970s. Furthermore, it was stated that bone marrow biopsy gets the better of bone marrow aspirates in diagnosis of bone marrow metastasis.  Anemia, thrombocytopenia, leukopenia, bi-cytopenia and pancytopenia can be encountered after the tumoral involvement of bone marrow. However, bone marrow metastasis could be established without any changes in hematologic parameters.  Bone marrow metastasis can be found in patients with widely metastatic solid tumors in addition to solid tumors firstly diagnosed by bone marrow biopsies.
In this study, clinical, hematological, and pathological features of 58 patients with bone marrow metastases diagnosed by bone marrow biopsies were examined retrospectively.
| Materials and methods|| |
We included 3345 bone marrow biopsies examined in Pathology Department of Our Hospital between January 2006 and August 2013 in this study. All of the bone marrow biopsies were performed through the crista iliaca posterior and stained with hematoxylin and eosin, Reticulin and Giemsa. Immunohistochemical staining were added according to patients' clinical and the biopsies' histopathological features and if there were a primary known tumor. The age, sex, primary diagnosis, changes in hematologic parameters, interval between primary diagnosis and bone marrow metastasis, and the median overall survival after bone marrow metastasis were retrospectively evaluated. Total count of leukocytes <4000/mm 3 , platelets <100.000/mm 3 , and the level of Hb <12 g/dl were accepted as leukopenia, thrombocytopenia, and anemia, respectively.
SPSS (Statistical Package for the Social Sciences, Chicago, IL) and Kaplan-Meier statistics were used for statistical analysis and the evaluation of survival, while Log-rank test was used for the comparison of the survival rates.
| Results|| |
A total number of 3345 bone marrow biopsies were examined. Fifty-eight patients, 32 female (55%) and 26 male (45%), with a mean age of 59.9 (range: 34-83) were diagnosed as bone marrow metastasis of solid tumors. Demographic, clinical, and laboratory characteristics of patients were shown in [Table 1]. Among these 58 metastatic cases, 39 (67.2%) had a primary diagnosis. Nineteen patients (32.8%) were firstly diagnosed from bone marrow biopsies as metastatic carcinomas. According to the primary tumor, the cases were grouped as breast cancer (n: 23, 59%), gastric cancer (n: 6, 15,3%), prostate cancer (n: 4, 10,2%) [Figure 1]a and b, lung cancer (n: 3, 7,7%) [Figure 1]c and d, nasopharyngeal cancer (n: 1, 2,6%), renal cancer (n: 1, 2,6%), and colon cancer (n: 1, 2,6%). From 58 patients with bone marrow metastasis, 39.7% had breast cancer, 32.8% had primary unknown tumor, 10.3% had gastric cancer, 6.9% had prostate cancer, 5.2% had lung cancer, 1.7% had colon cancer, 1.7% had renal cancer, and 1.7% had nasopharyngeal cancer. The median survival time after bone marrow metastasis was 28 days (95% confidence interval [CI]: 7.5-48.4) [Figure 2]. The median overall survival time of the patients with primary unknown tumor after bone marrow metastasis was 19 days (95% CI: 12.802-25.198). The median overall survival of the patients with primary known tumor was 30 days (95% CI: 12.360-47.640). The median overall survival difference was not statistically significant between patients with primary known and unknown tumor (P = 0.973) [Figure 3]. Forty-three of 46 patients whose follow-up data could be reached were dead while 3 were alive. The median survival time after the primary cancer diagnosis of these 46 patients were calculated as 575 days (95% CI: 216.6-933.3). The median time of bone marrow metastasis was found as 1077 days (95% CI: 381.260-1772.737). 19 (32.8%) cases were firstly diagnosed as malign by bone marrow biopsies. The median overall survival of patients with breast cancer, gastric cancer and prostate cancer were established as 80 days (95% CI: 41.959-162.240), 28 days (95% CI: 2.795-53.205) and 18 days (95% CI: 15.550-48.380), respectively. Statistically significant difference was observed between the survival of breast cancer and gastric cancer (P = 0.028). The median overall survival difference was not statistically significant between prostate cancer and gastric cancer (P = 0.475). The most common hematological findings were association of anemia and thrombocytopenia (31%), thrombocytopenia (27.6%) and anemia (20.6%), whereas other hematological changes were pancytopenia (12.1%) and leukopenia (3.4%). The median survival time of patients with thrombocytopenia was found as 26 days (95% CI: 13.764-38.236), while without thrombocytopenia as 80 days (95% CI: 54.101-186.038) and this difference was statistically significant (P = 0.042) [Figure 4]. The median overall survival of chemotherapy and nonapplicable patients with a known primary origin was 418 days (95% CI: 16.081-819.919) and 28 days (95% CI: 11.036-36.964) after bone marrow metastasis, respectively, and this difference was statistically significant (P < 0.005).
|Table 1: Demographic, clinical and laboratory characteristics of patients (n = 58)|
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|Figure 1: (a) Prostate adenocarcinoma metastasis to the bone marrow (H and E), (b) immunohistochemically prostate specific acid phosphatase positivity in prostate adenocarcinoma, (c) lung adenocarcinoma metastasis to the bone marrow (H and E), (d) immunohistochemically thyroid transcription factor-1 positivity in lung adenocarcinoma|
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|Figure 2: Median overall survival after the diagnosis of bone marrow metastasis|
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|Figure 4: Median overall survival (thrombocytopenia+ vs. thrombocytopenia−)|
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| Discussion|| |
Bone marrow biopsy is an easily applicable and accessible method in diagnosing metastatic solid tumors despite the discomfort of the procedure. Although magnetic resonance imaging and bone scintigraphy can give information about the spread of the disease; bone marrow aspiration and biopsy is more widely used in determining bone marrow metastasis because of the compatibility of histopathological and immunohistochemical examination.  However, the host elements of the bone marrow such as megakaryocytes, crushed cells of eritroid origin, osteoblastic and osteoclastic cells and stromal macrophages can be confused with nonhematopoietic originated malign cells.  However, immunohistochemical analysis can be performed on bone marrow biopsies in order to establish micrometastases and isolated tumor cells before the usual appearance of the histomorphological findings.  In addition to this, immunohistochemical markers can be applied for determining the primary origin of metastatic tumors. In metastatic breast cancers, the prognostic markers of estrogen and progesterone receptor and c-erb B2 can be reported by applying to bone marrow biopsies.
Bone marrow metastases can be seen in malignancies with known primary origin. Schmid et al. evaluated 1068 patients and found 17.8% of them as metastatic to bone marrow. In the same study, prostate, breast, lung, and gastric cancer were reported as the most common cancers metastasized to bone marrow.  Many different studies found similar results about the most common type of bone marrow metastasized cancers in adults, while Ewing sarcoma, rhabdomyosarcoma, and neuroblastoma were reported as the most common types in childhood. ,,, In our study, 3345 bone marrow biopsies were evaluated, and 58 (1.7%) of them were diagnosed as solid tumors metastatic to bone marrow. Breast, gastric and prostate cancers were found as the most common primary origins of bone marrow metastases similar with the literature. The low numbers of lung cancer cases metastasized to bone marrow was thought to be related to the nonexistence of the Department of Pulmonary Medicine in our Hospital.
Bone marrow metastasis affects the stage of the cancer and the time of survival. The median overall survival in patients known primary origins after the diagnosis of the primary tumor was found as 575 days. The median overall survival after a diagnosis of bone marrow metastasis was 28 days. Nineteen cases were firstly diagnosed as metastatic carcinomas with bone marrow biopsies in our study. In the study of Ringenberg et al., the median time of survival among 25 patients with unknown origin of bone marrow metastases was reported as 18 days.  In our study, among 19 patients, this duration was 19 days similar with the literature. In this study, the longest time of survival was obtained in metastatic breast cancer cases, 80 days, followed by gastric cancer, 28 days, and prostate cancer, 18 days. The difference between the median overall survival of breast and gastric cancers after a diagnosis of bone marrow metastasis was significant (P = 0.028), while gastric and prostate cancers did not show any significant difference (P = 0.475). The median overall survival of patients with primary known tumor was 30 days. The difference between the median overall survival of patients with primary unknown tumor and primary known tumor was not significant (P = 0.973). Kwon et al. evaluated 26 patients with bone marrow metastasis and found the median overall survival as 37 days. In the same study, the median overall survival times showed significant differences between chemotherapy applicable and nonapplicable patients, 121 days and 11 days, respectively (P < 0.001).  Kim et al. investigated 39 cases with bone marrow metastasis and reported the same significant difference between the chemotherapy applied and palliative care given patients as 67 days and 20 days, respectively with a P = 0.026.  In our study, patients with gastric cancer could not be treated with chemotherapy and the median overall survival of these patients was 28 days concordant with the literature. The median overall survival of chemotherapy and nonapplicable patients with a known primary origin was 418 days, and 28 days after bone marrow metastasis, respectively, and this difference was statistically significant (P < 0.005). Many differences in hematologic parameters can be frequently obtained in patients with bone marrow metastases. We found cytopenia by hemogram in 95% of our cases. In the study of Kilickap et al. including 73 patients with bone marrow metastasis, the median survival times of patients with thrombocytopenia and without thrombocytopenia were reported as 1-month and 13 months, respectively.  We found the same intervals as 26 and 80 days, and this difference was statistically significant (P = 0.042). The cause of the short survival time in patients with thrombocytopenia may be related to the risk of massive hemorrhage and poor administration of chemotherapy depending on the degree of thrombocytopenia.
| Conclusion|| |
Our study showed the necessity of bone marrow biopsy in patients with a doubt of bone marrow metastasis because of the applicability of chemotherapy in the early phases of the diseases when the patients could have higher performance status.
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Betul Bolat Kucukzeybek
Department of Pathology, Izmir Katip Celebi University Ataturk Training and Research Hospital, Izmir
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4]