Bone Marrow Carcinosis and Disseminated Tumour Cells

Abstract

to be deemed bone marrow carcinosis. Matrix bone metastases were demonstrated in 78% of patients with bone marrow carcinosis versus only 16% of the patients without bone marrow carcinosis. Heavy tumour infiltration of the bone marrow was associated with multiple bone lesions with histopathologic evidence of bone destruction [5]. This study provided evidence that the primary soil of metastatic bone disease in breast cancer is the bone marrow. Bone metastases are the result of invasion and destruction of bone tissue matrix mostly by tumour cells from within the marrow cavity. Intuitively, if bone marrow carcinosis heralds progression, the presence of even a small number of metastatic cells within the bone marrow should correlate with poor outcome. Disseminated carcinoma cells (DTCs) are clearly detectable in the bone marrow very early in the diagnosis of many solid tumours [6]. DTCs are distinct from frank bone marrow carcinosis as they are not associated with marrow dysfunction. However, clearly both exist on a continuum. Cells appear to disseminate from early primary lesions and then acquire additional genetic defects. Gene expression patterns of DTCs are often strikingly similar to the cells from the primary tumour [6]. The bone marrow may form the preferred reservoir for metastatic tumour cells, from where they re-circulate to distant organs where better growth conditions exist. The presence of DTCs in the bone marrow of primary breast cancer patients is an independent prognostic indicator of relapse, correlating with the appearance of bone metastases and with the occurrence of overt metastasis at other sites [7]. Significant correlations have been shown between DTCs in the bone marrow and metastatic relapse [8]. Animal models indicate that a significant proportion of DTCs remain dormant or perish, never developing into overt metastases [9]. Dormancy can be defined as slow-growing tumours that appear after long latency periods, quiescent tumours with no growth at all, or tumours that are in proliferaThe occurrence of overwhelming bone marrow infiltration by solid tumour cells is rarely reported. Despite the paucity of published data, this is not rare clinically and is often seen as a late-stage event. The article by Florcken and colleagues in the October 2009 issue of OnkOlOgie is indeed relevant [1]. The authors state that where bone marrow carcinosis has been reported it is usually associated with a large burden of disease, rapid progression and death. Yet there have been positive reports of long-term disease control in bone marrow carcinosis caused by solid tumours [2, 3]. The 63-year old female patient described by Florcken and colleagues died within 5 months of initial presentation [1]. The diagnosis of metastatic renal cell cancer was confirmed after investigation of thrombocytopenia. This is an unusual complication of renal cell cancer and to our knowledge the first reported case. Unexplained or progressive cytopenias in cancer patients should raise the possibility of bone marrow carcinosis. For patients without a cancer diagnosis, though other causes of bone marrow failure should be investigated, early bone marrow biopsy may help to diagnose the primary site of malignancy. Nuclear medicine bone scan and bone marrow biopsy are required to establish the diagnosis of disseminated carcinomatosis of the marrow. Bone scintigraphy commonly demonstrates a super-scan of malignancy. Bone marrow trephine generally exhibits the highest yield for detecting metastatic disease, as aspiration may prove unsuccessful due to fibrosis [4]. The marrow serves as a reservoir of tumour cells with the potential to metastasise. The physical burden of tumour cells within the bone marrow may eventually interfere with haematopoiesis, haemostasis and immune responses. Bone marrow carcinosis then becomes clinically significant, often compounded by myelosuppressive cytotoxics. The incidence of bone marrow carcinosis was investigated in 380 breast cancer patients at the time of first recurrence. 87 patients (23%) had sufficient tumour cells in the bone marrow