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Turkish Journal of Cancer
2007, Volume 37, Number 3, Page(s) 085-088
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Bone marrow metastasis of solid tumors: Clinicopathological evaluation of 73 cases
SAADETTİN KILIÇKAP, MUSTAFA ERMAN, MURAT DİNÇER, SERCAN AKSOY, HAKAN HARPUTLUOĞLU, ŞUAYİB YALÇIN
Hacettepe University Institute of Oncology, Department of Medical Oncology, Ankara-Turkey
Keywords: Solid tumor, metastasis, bone marrow, aspiration
Summary
The aim of this study was to investigate the clinical characteristics of adult patients with BM metastases of solid tumors diagnosed by bone marrow (BM) aspiration. In this retrospective study, we reviewed the results of 3842 BM aspirations carried out in the Medical Oncology Unit in Hacettepe University between January 1993 and December 2004. Basic clinical characteristics of patients as well as sites of metastases and complete blood counts were obtained from the hospital records. Statistical analyses were performed using Statistical Package for Social Sciences (SPSS) for Windows version 10.0. Seventy-three patients (1.9%) had evidence of involvement of the BM by a solid tumor. Thirty-six patients were male (49.3%) and 37 were female (50.7%). Mean age was 49í└13 (min: 17, max: 77). Breast cancer (28.8%) and lung cancer (23.3%) were the most common cancers associated with a BM metastasis. At the time of diagnosis, 68.5% of patients were found to have anemia, 58.9% thrombocytopenia, and 23.3% neutropenia. The most common site of metastasis associated with BM involvement was bone (n=51, 70.8%). Median survival after the diagnosis of BM metastasis was found to be 5 months and one-year survival was 28%. Patients with thrombocytopenia had significantly shorter median survival than patients with normal thrombocyte counts (1 month vs. 13 months, respectively; p <0.0001). BM involvement by solid tumors carries a poor prognosis, especially when thrombocytopenia is present. [Turk J Cancer 2007;37(3):85-88]
  • Top
  • Summary
  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
  • Introduction
    Though bone marrow (BM) involvement is most commonly seen with myeloid or lymphoid hematological malignancies, solid tumors may also spread to the BM via the hematogenous route. Presenting signs and symptoms are usually related to cytopenias and include fatigue, dizziness, orthostatic hypotension, bleeding and infections. The latter two are known to result in substantial morbidity and even mortality in this group of patients. Therefore, BM metastasis is almost universally a poor prognostic factor [1]. Imaging techniques like radionuclide bone scan, magnetic resonance and computed tomography are usually ineffective and BM aspiration and biopsy remain the procedures of choice to document BM involvement [2,3]. BM aspiration can be carried out in a matter of minutes, and histomorphological examination by Wright or Giemsa stain can be completed in an additional hour. It therefore is the fastest, easiest and cheapest method to search for metastatic foci in the BM. In this report, we have investigated the clinical characteristics of seventythree adult patients with BM metastases of solid tumors diagnosed by BM aspiration.
  • Top
  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
  • Material and Methods
    We reviewed the results of BM aspirations carried out in the Medical Oncology Unit in Hacettepe University between January 1993 and December 2004. This unit is one of the largest medical oncology centers in Turkey, and all kinds of solid tumors as well as hematological malignancies are diagnosed and treated. In the daily practice, BM aspirations are performed from the posterior iliac crests and are accompanied by trephine biopsies, unless deemed clearly unnecessary. Aspiration specimens are stained with Wright stain and at least 3 smears are examined by experienced hematooncologists.

    In this retrospective study, the results of 3842 BM aspirations were examined. Those with involvement of hematological malignancies were excluded and those with metastases of solid tumors were recorded. Confirmation by histopathological examination of trephine biopsies was also required. Basic clinical characteristics of patients as well as sites of metastases and complete blood counts were obtained from the hospital records. Anemia was de- fined as Hb value ≤12 gr/dL thrombocytopenia as platelet count below 150,000/mm3 and neutropenia as white blood cell count (WBC) lower than 3500/mm3. The central tendency of numerical variables like age, hemoglobin, thrombocyte and WBC counts are given as meaní└standard deviation (SD). Overall survival following the diagnosis of BM metastasis was calculated using the Kaplan-Meier method. The comparison of the survival of subgroups was carried out by the log-rank test. Statistical analyses were performed using Statistical Package for Social Sciences (SPSS) for Windows version 10.0.

  • Top
  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
  • Results
    We reviewed the results of 3842 BM aspirates carried out in our institute from January 1993 to December 2004. Seventy-three patients (1.9%) had evidence of involvement of the BM by a solid tumor. Thirty-six patients were male (49.3%) and 37 were female (50.7%). Mean age was 49í└13 (min: 17, max: 77). Clinical characteristics of the patients are summarized in table 1.

    Table 1: Clinical characteristics of the patients

    Breast cancer (28.8%) and lung cancer (23.3%) were the most common cancers associated with a BM metastasis, followed by gastric cancer (9.7%), prostate cancer (6.8%), and Ewing sarcoma (6.8%). No primary tumor site could be detected in 7 patients (8.2%) with BM metastasis. Less frequent sites included soft tissue sarcoma (2.7%), nasopharyngeal carcinoma (2.7%), malignant melanoma (2.7%), medulloblastoma (1.4%), and cancers of the larynx (1.4%), bladder (1.4%), rectum (1.4%), endometrium (1.4%), and testis (1.4%). The diagnosis of BM metastasis coincided with the diagnosis of the primary tumor in 35 patients (47.9%). Histopathological diagnoses of the patients are given in table 2.

    Table 2: Primary diagnoses of the patients

    At the time of diagnosis, 68.5% of patients were found to have anemia, 58.9% thrombocytopenia, and 23.3% neutropenia. Blood counts were normal in 13.7% of patients, while 17.8% had pancytopenia. Anemia and thrombocytopenia were present in 23.3% of patients, while only 2.7% had anemia and leukopenia and 1.4% had leukopenia and thrombocytopenia. Mean hemoglobin level was 10.5í└2.5 g/dl (min: 5.8, max: 16.5), WBC 7,900í└6,600/mm3 (min: 2,200, max: 44,800), and platelet 180,000í└163,000/mm3 (min: 9,000, max: 837,000). The hematological parameters of the patients at the time of diagnosis are summarized in table 3.

    Table 3: Hematological parameters of the patients at the time of diagnosis

    The most common site of metastasis associated with BM involvement was bone (n=51, 70.8%). Other sites included liver (16.7%), brain (9.5%), lungs (9.5%), adrenal glands (5.5%), soft tissues (2.7%), orbita (1.4%), kidney (1.4%) and breast (1.4%). Other sites of metastasis associated with BM involvement are summarized in table 1. Median survival after the diagnosis of BM metastasis was found to be 5 months (95% CI: 1.0-9.0) and one-year survival was 28% (Figure 1). Patients with thrombocytopenia had significantly shorter median survival than patients with normal thrombocyte counts (1 month vs. 13 months, respectively; p<0.0001) (Figure 2).

    Fig 1: Overall survival in patients with bone marrow metastasis

    Fig 2: Overall survival of patients with thrombocytopenia

  • Top
  • Introduction
  • Methods
  • Results
  • Disscussion
  • References
  • Discussion
    Though not very frequent, BM is one of the important sites of metastasis of solid tumors. The involvement of the BM is not only a sign of diffuse hematogenous spread of the tumor; it also results in cytopenias that increase the risk of bleeding and infection. Cytopenias also hinder the delivery of effective anti-neoplastic treatment, as almost all chemotherapeutics have at least some degree of hematotoxicity. All these factors add up to yield a worse prognosis for the patient who has BM metastasis.

    Magnetic resonance imaging can give some clues on the involvement of BM and the definitive diagnosis depends on histopathological examination of BM biopsies. Immunohistochemical studies as well as molecular techniques like polymerase chain reaction have enabled us to detect metastatic cells in the BM, even if they are in minute quantities [4]. Though these methods are gaining popularity, they require much more effort, time and money than the conventional techniques. The clinical significance of microscopical involvement of the BM also remains to be established. Morphological examination of the BM aspiration is much less sensitive than the latter methods, yet it remains the easiest, cheapest and least time consuming procedure for the diagnosis of clinically suspected BM involvement.

    Theoretically, all tumors can metastasize to the BM, however, cancers of the breast, prostate and lung are the most frequently encountered ones in adults [5-7]. In pediatric cases, neuroblastoma is responsible for the majority of cases. In a retrospective study, Mohanty et al. [6] showed that prostate cancer (47.8%) was the most common tumor among adults, followed by breast cancer (28.2%). In this series, all pediatric cases had neuroblastoma. In another study, these findings were confirmed: Neuroblastoma was the most common primary tumor in children, followed by breast and prostate cancers in adults [8].

    In our study, we reviewed the results of 3842 patients who had a BM aspiration. We found 73 cases with BM metastasis of solid tumors. Breast and lung cancers were the most commonly encountered tumors. In contrast to the literature, we had only 5 cases of prostate cancer (6.8%). Though this may at least in part be due to a lower incidence of prostate cancer in our country than in more developed countries, it probably results from the small number of patients followed in our clinic, as most prostate cancer patients are treated by urologists in our country.

    Patients with BM involvement could have normal blood counts, some disturbances in one or more series or they could be pancytopenic. Though severe anemia can be lifethreatening, the complications of neutropenia and thrombocytopenia result in more morbidity and mortality. Pancytopenic patients are known to have a higher complication risk than the others. In a study, the authors have reported six cases with tumors metastatic to the BM [8]. Of these, 4 patients (67%) had anemia, 5 (83%) had thrombocytopenia and 3 (50%) had leucopenia. In our study, the figures that we have observed are somewhat smaller: Anemia was observed in 68.5%, leukopenia in 23.3% and thrombocytopenia in 58.9% of the patients, while 17.8% of patients had pancytopenia, 37.4% bicytopenia, and %13.9 had normal counts. These findings suggest that in our institution, bone marrow aspiration is done in patients with less profound hematological disturbances.

    Median survival of the patients with thrombocytopenia was significantly shorter than those without thrombocytopenia. This finding may be related to amount of bone marrow involvement, long lasting recovery of thrombocytopenia that leads to hemorrhagic complications and death.

    The four parameters, which are strongly correlated with marrow involvement, were the leukoerythroblastic blood pattern, a serum lactic dehydrogenase over 500 IU/liter, a platelet count under 100,000/microliter, and bone pain [9].

    BM involvement by solid tumors carries a poor prognosis, especially when thrombocytopenia is present. Aspiration of the BM provides an easy and quick way of detecting involvement, however, biopsy with immunohistochemical and/or molecular techniques may be needed in case of microscopical tumor burden.

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  • Introduction
  • Methods
  • Results
  • Discussion
  • References
  • References

    1) Diel IJ, Kaufmann M, Goerner R, et al. Detection of tumor cells in bone marrow patients with primary breast cancer: a prognostic factor for distant metastasis. J Clin Oncol 1992;10:1534-9.

    2) Bearden JD, Ratkin GA, Coltman CA. Comparison of the diagnostic value of bone marrow biopsy and bone marrow aspiration in neoplastic disease. J Clin Pathol 1974;27:738-40.

    3) Singh G, Krause JR, Breitfeld V. Bone marrow examination for metastatic tumor: aspirate and biopsy. Cancer 1977;40:2317-21.

    4) Zippelius A, Pantel K. RT-PCR-based detection of occult disseminated tumor cells in peripheral blood and bone marrow of patients with solid tumors. An overview. Ann N Y Acad Sci 2000;906:110-23.

    5) Wong KF, Chan JK, Ma SK. Solid tumor with initial presentation in the bone marrow: a clinicopathologic study of 25 adult cases. Hematol Oncol 1993:11;35- 42.

    6) Mohanty SK, Dash S. Bone marrow metastasis in solid tumors. Indian J Pathol Microbiol 2003;46:613-6.

    7) Sharma S, Murari M. Bone marrow involvement by metastatic solid tumors. Indian J Pathol Microbiol 2003;46:382-4.

    8) Sari R, Aydogdu I, Ozen S, et al. Metastatic bone marrow tumors: a report of six cases and review of the literature. Haematologia 2001;31:215-23.

    9) Chernow B, Wallner SF. Variables predictive of bone marrow metastasis. Cancer 1978;42:2373-8.

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