Bone Marrow Involvement by Cancer

A 48 year old women presented with backache. The MRI suggested the presence of a metastatic involvement of multiple vertebrae. The biopsy from D11 showed it to involved by an estrogen and progesterone positive breast cancer. The X ray showed pulmonary metastasis. Treatment was initiated with combination of epirubicin, cyclophsophamide and fluorouracil with zolandronate. After the fourth cycle her haemogram showed a haemoglobin of 9.2g/dL, leucocyte count of 11.7 X 10,9/L and a platelet count of 80X109/L. and thrombocytopenia. The peripheral smear showed a differential leucocyte count was 65% polymorphonuclear neutrophils, 21% lymphocytes, 3% eosinophils, 3% monocyte, 2% myelocytes, 1% metamyelocytes and 5% band forms. Nucleated red cells were seen. A bone marrow aspiration and trephine biopsy was performed from the right iliac crest.

The aspirate was scanty and has paucity of particles. The microscopic examination showed infiltration by carcinoma. This was confirmed on the trephine biopsy. The cells were found to be expressing estrogen and progesterone receptors. The images of the bone marrow aspirate are shown below.

Figure 1. A breast carcinoma cell in the bone marrow

Figure 2. A breast carcinoma cell with two neutrophils

Figure 3. Breast carcinoma cells with an orthochromatophilic normoblast

Bone marrow involvement by cancers is common. Common cancers involving the bone marrow in adults include cancers of the breast, prostate and lung. Neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma, primitive neuroectodermal tumors and retinoblastomas are the common childhood tumors involving the bone marrow.

Bone marrow infiltration manifests with hematological anomalies. Leucoerythroblastic anaemia when present is most suggestive of bone marrow involvement. It is neither sensitive nor specific and is absent in about half the patients. About 70% of the patients have concomitant bone involvement and symptoms of metastatic bone disease – bone pain, fractures and hypercalcaemia may be present.

The diagnosis is made by a bone marrow aspiration and biopsy. Sensitivity of bone marrow aspiration for diagnosing bone marrow involvement be cancer is  28% and that of trephine biopsy is 35-45%. The diagnostic yields are better  increased by examining more films examinations of clotted areas, taking multiple biopsies or one large biopsy; 75% of the trephine biopsies show aspirate positive; she patients show normal trephine and abnormal cells on the smear; both should be performed

Bone marrow involvement has been shown to be an adverse prognostic marker for breast cancer. The impact of bone marrow involvement in other cancers in not known. Bone marrow cells can survive chemotherapy and remain dormant for long periods (Int J Cancer 2008 Nov 1;123(9):1991-2006). The role of bone marrow metastasis in other cancers is not clear though there are suggestions that they may affect prognosis of prostate cancer (Adv Urol. 2012; 2012: 135281) colorectal cancer (Br J Cancer  2011 Apr 26;104(9):1434-9)

Manifestations:

Circulating tumor cells were first reposted by ash worth in 1869.

Immunomagnetic capture using antibodies against epithelial cell surface molecule EpCam

SWOG conducting a study to determine the utility of changing therepay of breast cancer depending on the response of CTC to one cycle of chemotherapy

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