Bone Marrow Metastases: A Survey of Nonhematologic Metastases With Immunohistochemical Study of Metastatic Carcinomas
With current therapies and imaging methods, staging bone marrow biopsies, and subsequently found metastases to the bone marrow, are less frequent. Historically, the most common metastatic nonhematologic tumors to the bone marrow in adult and pediatric patients included breast carcinoma, neuroblastoma, prostatic carcinoma, Ewing sarcoma, and lung tumors. Although the staining patterns of these primary tumors have been extensively examined, the utility of these immunohistochemical profiles has not been studied in the context of metastatic lesions to the bone marrow. In our review of 111 metastases to the bone marrow over an 18-year period, the most common primary tumor types are, in order of frequency: breast carcinoma, neuroblastoma, lung tumors, rhabdomyosarcoma, Ewing sarcoma, prostate carcinoma, and gastrointestinal tract tumors. Additionally, in an analysis of 44 adult metastatic carcinomas, we confirm that immunohistochemical panels are useful in identifying the primary tumor site. Overall, the immunohistochemical characterization of metastatic carcinomas to the bone marrow show good correlation with the established staining pattern of the primary tumors.
Available from: PubMed Central
- "Metastatic carcinoma in bone marrow in the exhaustion phase is a rare pathophysiological form of bone marrow metastasis. Featuring rapid onset, progressive anemia, and thrombocytopenia accompanied by severe hemorrhage, infection, and even disseminated intravascular coagulation (DIC), it is considered a lethal complication of malignant tumor [8-10]. Due to the poor performance status, systemic chemotherapy is often considered a relative contraindication for such patients. "
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ABSTRACT: Primary bronchial mucoepidermoid carcinoma in the lung is relatively rare. It rarely presents with the highly malignant biological characteristic of bone marrow metastasis. We describe a case of this disease with bone marrow metastasis. A 56-year-old man with the primary manifestation of bone pain and bloodstained sputum had two abnormal shadows on the left inferior lobar bronchus and peripheral tissue of the lower lobe of the left lung, respectively. Computed tomography-guided percutaneous puncture biopsy and bone imaging confirmed the diagnosis of high-grade bronchial mucoepidermoid carcinoma with bone metastasis. However, the patient soon presented with progressive hemoglobin and platelet decline and severe multi-organ hemorrhage. Subsequently, we performed bone marrow aspiration and biopsy, which revealed malignant cells and necrosis. The patient deteriorated rapidly from the disease, and died on the 16th day of admission. We hope that this case report will increase awareness of the possibility of primary high-grade bronchial mucoepidermoid carcinoma metastasizing to the bone marrow, which might be a poor prognostic factor.
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ABSTRACT: The treatment of bone metastases in breast cancer is traditionally based upon the receptor status of the primary tumour. However, retrospective studies have shown significant discordance in receptor expression between primary and metastatic tumours. Therefore, the aim of this study was to prospectively assess the incidence of discordant receptor status in primary and metastatic disease and evaluate the role of bone marrow biopsies for the reassessment of receptor status.
Nine patients with known bone metastases were assessed with both a radiologically guided bone biopsy and a bone marrow aspirate and trephine. The oestrogen receptor and progesterone receptor status of these samples was assessed and compared with the primary breast cancer. Bone and bone marrow samples were also evaluated for HER2/neu status and compared with the status of the primary tumour if available.
Tumour cells were found in six of the nine bone metastasis specimens and five of the nine bone marrow samples. A discordance rate for the oestrogen receptor was seen in five of nine patients (56%) and for the progesterone receptor in four patients (44%). There seemed to be a correlation between bone and bone marrow biopsies.
The receptor discordance rate in this study was similar to previous retrospective studies. It seems that bone marrow biopsy may be a simple, safe and well-tolerated way to obtain tissue to reassess the receptor status of metastatic breast cancer.
Available from: Giridhar Mudduluru
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ABSTRACT: Extracellular matrix metalloprotease inducer (EMMPRIN) induces matrix metalloproteinase (MMP) expression, tumor-stroma cell interaction, and invasion/angiogenesis. The objectives of the current study were to find the first evidence of a prognostic impact of total and relative EMMPRIN expression in colorectal cancer cells and to analyze EMMPRIN in bone marrow-disseminated tumor cells and normal cells from 2 different gastrointestinal cancer entities.
Tumors and normal tissues from 40 patients with colorectal cancer who were followed prospectively (median follow-up, 31 months) were analyzed for EMMPRIN by immunohistochemistry. Bone marrow from 51 patients (13 patients with gastric cancer and 38 patients with colorectal cancer) with evidence of disseminated tumor cells was screened for EMMPRIN in tumor cells and normal cells (cytokeratin 18/EMMPRIN double immunocytochemistry).
A significant correlation between poor disease-specific survival (P=.037; Kaplan-Meier method; Mantel-Cox log-rank tests) and an increased ratio of EMMPRIN in tumor cells versus corresponding normal epithelial cells were observed. Furthermore, the relative increase of EMMPRIN was associated with a trend toward poor overall and recurrence-free survival. High relative EMMPRIN expression was associated significantly with positive metastasis status (M1) (P=.001) and with a trend towards advanced pathologic tumor classification. Sixteen percent of disseminated tumor cells in bone marrow samples from patients with colorectal cancer and 48.5% of disseminated tumor cells in bone marrow samples from patients with gastric cancer stained positive for EMMPRIN, and EMMPRIN on micrometastatic cells was associated significantly with parameters of tumor progression (M status, noncurative resectability). A minority of normal bone marrow cells were stained for EMMPRIN, suggesting their suitability for molecular targeting.
To the authors' knowledge, this study was the first to indicate that increased relative EMMPRIN protein in tumor-specific cells compared with normal cells predicts poor disease-specific survival in patients with colorectal cancer and that EMMPRIN in primary and bone marrow-disseminated tumor cells is associated with clinical markers of tumor progression in patients with colorectal/gastric cancer.
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