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Metastatic lobular carcinoma of the breast: patterns of spread in the chest, abdomen, and pelvis on CT.

OBJECTIVE: We determined the pattern of spread of metastatic lobular carcinoma in the chest, abdomen, and pelvis on CT. MATERIALS AND METHODS: We identified 57 women (age range, 30-79 years; mean age, 57 years) with metastatic lobular carcinoma of the breast who underwent CT of the chest, abdomen, or pelvis between 1995 and 1998. Then two experienced oncology radiologists retrospectively reviewed 78 CT examinations of those patients to identify sites of metastatic disease and to identify complications caused by metastases. RESULTS: Metastases were identified in bone in 46 patients (81%), lymph nodes in 27 patients (47%), lung in 19 patients (33%), liver in 18 patients (32%), peritoneum in 17 patients (30%), colon in 15 patients (26%), pleura in 13 patients (23%), adnexa in 12 patients (21%), stomach in nine patients (16%), retroperitoneum in nine patients (16%), and small bowel in six patients (11%). Eighteen patients (32%) had gastrointestinal tract involvement that manifested as bowel wall thickening. Hydronephrosis was present in six patients (11%). CONCLUSION: Although lobular carcinoma metastasized to common metastatic sites of infiltrating ductal carcinoma, lobular carcinoma frequently metastasized to unusual sites, including the gastrointestinal tract, peritoneum, and adnexa. Gastrointestinal tract involvement was as frequent as liver involvement, appearing as bowel wall thickening on CT. Hydronephrosis was a complication of metastatic lobular carcinoma.

Abdominal Neoplasms↗

Sonographic patterns of ribs with tumor involvement.

We analyzed the sonographic appearance of the ribs when there was tumor involvement in 16 patients (12 men and 4 women). The tumors included 11 carcinomas, 3 nonepithelial malignancies and 2 benign tumors. Three sonographic patterns on the cross section of abnormal ribs were identified. Pattern I was an eccentrical hyperechoic plate-like shadow inside a hypoechoic tumor. Pattern II was a round hyperechoic shadow or ring in the center of a hypoechoic tumor. Pattern III was a hypoechoic tumor only. The Pancoast tumor manifested pattern I. Metastatic cancer, mostly squamous cell carcinoma, manifested pattern II, and both malignant and benign tumors could manifest pattern III. In sonography, the margin and shape of the tumors, the change in the acoustic shadow of the rib and the pleural line did not differentiate the malignant tumors from benign tumors. When we routinely took a biopsy of these tumors under sonar guidance, the diagnostic yield was 100% without any complications. We conclude that the rib should be evaluated in chest sonography, and that pattern recognition and biopsy under sonar guidance are most useful.

Adult↗

[Lipid composition of human malignant brain tumors].

Malignant transformation is characterized by the uncontrolled proliferation of cells. And changes in the composition of glycolipids, cell surface component which may be involved in regulation of cell growth, were often observed in the malignant transformation. In this study, cholesterol, lipid-bound phosphorus, cerebroside, sulfatide and ganglioside were quantitated in the tissue of 20 human malignant brain tumors (malignant glioma, 8; low grade glioma, 4; metastatic tumor, 7; malignant meningioma, 1). As compared with normal brain, all tumor tissue contained lower cholesterol, sialic acid, cerebroside and sulfatide. Metastatic brain tumor or glioma showed characteristic patterns in the content of ganglioside, cerebroside and sulfatide respectively. The ganglioside patterns of metastatic tumor or glioma contained a greater proportion of structurally simpler gangliosides than normal brain. And in metastatic tumor, GM3 was a major ganglioside. On the contrary, glioma had increased proportion of GM3 and GD3 gangliosides. High grade glioma such as Grade 3-4 contained higher proportion of GM3 and GD3, whereas low grade glioma (Grade 1-2) contained less proportion of GM3 and GD3.

Brain Neoplasms↗

Metastatic risk for distinct patterns of postirradiation local recurrence of posterior uveal melanoma.

OBJECTIVE: The purpose of the study is to compare the prognostic significance of horizontal/marginal versus vertical/diffuse patterns of postirradiation local recurrence of posterior uveal melanoma. DESIGN: The study design was a nonrandomized, retrospective clinical study. Semiparametric and nonparametric statistical techniques were used. PARTICIPANTS: Seven hundred sixty-six posterior uveal melanoma patients were studied. INTERVENTION: Either iodine-125 plaque or helium ion radiation therapy was performed. MAIN OUTCOME MEASURES: Local tumor recurrence and systemic metastasis were measured. RESULTS: Local tumor recurrence was detected in 66 (8.6%) of 766 irradiated tumors. The 5-year actuarial rate of local recurrence was 10%. The recurrence pattem was horizontal/marginal in 27 patients (41%) and vertical/diffuse in 39 patients (59%). Systemic metastasis was detected in 5 patients (19%) with horizontal/marginal recurrence and in 19 patients (49%) with vertical/diffuse recurrence. After known metastatic risk factors were controlled, the relative risk for metastasis was 2.2 for horizontal/marginal recurrence and 5.1 for vertical/diffuse recurrence (P = 0.05). The actuarial rate of systemic metastasis was 2.9% per year for all patients, 6.3% per year for patients with horizontal/marginal recurrence, and 15.5% per year for patients with vertical/diffuse recurrence. CONCLUSIONS: Postirradiation local recurrence of posterior uveal melanoma is a risk factor for systemic metastasis. Vertical/diffuse recurrences may be associated more strongly with metastatic disease than horizontal/marginal recurrences.

Adult↗

Osteoblasts produce soluble factors that induce a gene expression pattern in non-metastatic prostate cancer cells, similar to that found in bone metastatic prostate cancer cells.

BACKGROUND: Progressive prostate cancer typically metastasizes to bone where prostate cancer cells gain an osteoblast-like phenotype and induce osteoblastic metastases through unknown mechanisms. To investigate the biology of prostate cancer skeletal metastases, we compared gene expression between the non-metastatic LNCaP cell line and its derivative cell line C4-2B that metastasizes to bone. METHODS: Total RNA from LNCaP and C4-2B cell lines was isolated and used to probe membrane-based gene arrays (Comparison 1). Additionally, LNCaP cells were incubated in the absence or presence of conditioned media (CM) from a human osteoblast-like cell line (HOBIT) and total RNA from these cells was used to probe gene arrays (Comparison 2). Differential expression of genes was confirmed by RT-PCR. RESULTS: Of the 1,176 genes screened, 35 were differentially expressed between LNCaP and C4-2B cells (Comparison 1). HOBIT-CM induced differential expression of 30 genes in LNCaP cells (Comparison 2). Interestingly, 19 genes that were differentially expressed in C4-2B vs. LNCaP also displayed a similar expression pattern in LNCaPs grown in HOBIT-CM. These genes are primarily involved in motility, metabolism, signal transduction, tumorigenesis, and apoptosis. CONCLUSIONS: These results suggest that osteoblasts produce soluble factors that contribute to the progression of prostate cancer skeletal metastases, including their transition to an osteoblast-like phenotype. Additionally, these data provide targets to explore for further investigations towards defining the biology of skeletal metastases.

Bone Neoplasms↗

CXCR4 expression in neuroblastoma primary tumors is associated with clinical presentation of bone and bone marrow metastases.

BACKGROUND/PURPOSE: The chemokine receptor, CXCR4, has been implicated in the mechanism of tumor cell metastasis to bone and bone marrow. Neuroblastoma, a cancer of children, is well known for its potential to metastasize to these sites. The goal of this study was to investigate whether the degree of expression of CXCR4 on cells from neuroblastoma primary tumors was related to the pattern of metastatic involvement. METHODS: Archived neuroblastoma primary tumor samples and clinical data were collected from 26 patients with newly diagnosed neuroblastoma. Expression of CXCR4 (12g5 antibody) was evaluated on formalin-fixed paraffin-embedded tumor tissues using standard immunohistochemical techniques. Each tumor was graded (grade 1 through 4) based on the proportion of cells that were positive for the 12g5 antibody. Tumor grades for CXCR4 expression were compared with clinical data from each patient. RESULTS: Higher grades of expression (grade 3 and 4) were found in tumors from patients with high-stage disease (P < .01) and in patients with bone and bone marrow metastases (P < or = .01). Clinical outcome in patients with tumors highly expressing CXCR4 was significantly worse (P < .01) than in those patients with low-grade CXCR4. CONCLUSIONS: CXCR4 expression in neuroblastoma primary tumors is significantly correlated with the pattern of metastatic spread.

Abdominal Neoplasms↗

Patterns of disease spread in metastatic breast carcinoma: influence of estrogen and progesterone receptor status.

BACKGROUND AND PURPOSE: It is widely recognized that tumor hormone receptor status correlates with overall survival in metastatic breast carcinoma; however, the influence of hormone receptors on the pattern of disease spread is not well known. PURPOSE: We set out to determine the common distributions of metastatic disease spread in metastatic breast carcinoma, and to evaluate tumor hormone receptor status as predictor of disease spread. METHODS: Thirty-six patients being imaged for possible metastatic breast carcinoma between 1995 and 1998, in whom the presence or absence of tumor estrogen and progesterone receptors (ER+ or ER- / PR+ or PR-) was known, who underwent both contrast-enhanced MR of the brain and total body skeletal scintigraphy, were studied retrospectively. RESULTS: Of twelve patients with skeletal metastases but no brain metastases, 83% were ER+/PR+. Ten patients had brain metastases but no skeletal involvement, 80% of which were ER-/PR-. Seven patients had no brain or osseous metastases, but had metastatic disease in the chest or abdomen. Eighty-six percent of patients in this group were ER-/PR-. The tumor receptor status was statistically different between these three distribution groups (P = .01). A final group, consisting of seven patients, showed widespread disease, with diffuse metastases to the brain, viscera, and skeleton. In this group, no patients were ER+/PR+. CONCLUSION: There are two major patterns of disease spread in metastatic breast carcinoma, excluding patients with extensive diffuse metastases. Patients with ER+/PR+ tumors tend to develop osseous but not brain metastases. Patients with ER-/PR- tumors tend to develop brain but not osseous metastases. Appreciation of these distributions can aid the radiologist in detecting metastatic lesions, and will help the clinician to estimate the likelihood of metastases to various organ systems, as well as to potentially target therapy.

Bone Neoplasms↗

Patterns of care for metastatic carcinoma of the prostate gland: results of the American College of Surgeons' patient care evaluation study.

The annual incidence of prostate cancer more than doubled between 1984 and 1990, increasing from an estimated 76 000-200 000 cases respectively. Part of this increase may have been the result of increased detection. This study utilizes data from an American College of Surgeons Patient Care Evaluation (PCE) study to report on changes in the management of metastatic disease. Approximately 2000 hospitals were invited to submit data on a standard collection form designed by a multidisciplinary committee of specialists. Data were received from 730 hospitals on 14 716 patients with newly diagnosed cancer of the prostate in 1984, and from 1035 hospitals for 23 214 patients in 1990. Between 1984 and 1990 there was a decrease in the percentage of reported patients diagnosed with Stage IV disease, falling from 25.3-21.2%. The number of patients receiving a prostate specific antigen (PSA) test increased from 6.3-74.8% and the proportion of abnormal PSA results increased from 82-92.7%. The proportion of patients diagnosed by transurethral resection of the prostate (TURP) and perineal biopsy decreased, while an increase was noted in the proportion of men diagnosed by transrectal biopsy and transrectal ultrasound (TRUS). Treatment by orchiectomy alone increased from 31.8-40.7% of patients, while the administration of exogenous hormone therapy alone declined from 22.3-14.9% of patients. Two and five-year survival rates for the most common forms of therapy were 56.7% and 22.5% respectively for orchiectomy, 57% and 24.6% respectively for exogenous hormone therapy, and 50.3% and 23.5% respectively for no cancer directed therapy. Following a second course of therapy, the two-year survival rate for patients receiving a subsequent orchiectomy was 36.7 vs 17.8% for those receiving secondary exogenous hormone therapy. The percentage of patients diagnosed with Stage IV disease has decreased while prostate cancer diagnoses are being made more frequently utilizing the PSA test and TRUS biopsies. Hormone treatment remains the most common form of therapy with either orchiectomy or exogenous hormone therapy having higher survival rates than other common treatment modalities.

Journal Article↗

Gene expression patterns associated with the metastatic phenotype in rodent and human tumors.

Using subtractive technology, we have generated metastasis-associated gene expression profiles for rat mammary and pancreatic adenocarcinomas. Several genes whose expression is thought to be related to tumor progression such as c-Met, urokinase-type plasminogen activator receptor, ezrin, HMG-1, oncomodulin, cathepsin, and caveolin were thereby isolated. Half of the metastasis-associated clones showed no significant homology to genes with known function. Notably, several of the metastasis-associated clones were also expressed in metastatic lines but not in nonmetastatic lines of other tumor models. Furthermore, in situ hybridization using selected clones documents the relevance of these results for human cancer because strong expression in tumor cells including metastases was detected in human colorectal cancer samples and, to a lesser extent, in mammary cancer samples. These data support the concept that tumors express a "metastatic program" of genes.

Animals↗

Randomized trial of cyclophosphamide, doxorubicin, and 5-fluorouracil alone or alternating with a "cycle active" non-cross-resistant combination in women with visceral metastatic breast cancer: a Southeastern Cancer Study Group project.

Patients with visceral patterns of metastatic breast cancer were stratified according to dominant metastatic site and performance status and then randomized to therapy with cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) or CAF alternating with a "cell-cycle active" regimen including cytosine arabinoside, methotrexate with leucovorin rescue, and oncovin ( CAMELEON ). One hundred eighty-seven patients were randomized; response rate for CAF was 44% and for CAF + CAMELEON , 40%. Durations of disease control and survival were not significantly different. Toxicity of CAF was as anticipated with predominant granulocytopenia, vomiting, and alopecia. Toxicity of CAMELEON was less severe than that of CAF, and CAF toxicity was not worsened by preceding courses of CAMELEON ; however, the CAF- CAMELEON regimen was cumbersome and complex leading to both physician and patient noncompliance. Contrary to the preliminary results of a pilot study, and preliminary reports of the present trial suggesting benefit for the CAF- CAMELEON regimen the present randomized trial does not confirm any significant benefit of CAF- CAMELEON over CAF alone in patients with visceral metastatic breast cancer although this conclusion must be viewed in light of the high inevaluability rate due to patient and physician noncompliance.

Agranulocytosis↗

Spontaneous tumors in dogs and cats: models for the study of cancer biology and treatment.

Spontaneous tumors in dogs and cats are appropriate and valid model tumor systems available for testing cancer therapeutic agents or studying cancer biology. The pet population is a vastly underutilized resource of animals available for study. Dogs and cats develop spontaneous tumors with histopathologic and biologic behavior similar to tumors that occur in humans. The tumors with potential relevance for human cancer biology include osteosarcoma, mammary carcinoma, oral melanoma, oral squamous cell carcinoma, nasal tumors, lung carcinoma, soft tissue sarcomas, and malignant non-Hodgkin's lymphoma. Canine osteosarcoma is a malignant aggressive bone tumor with a 90% metastasis rate after surgical amputation. Its predictable metastatic rate and pattern and its relative resistance to chemotherapy make this tumor particularly attractive for studying anti-metastasis approaches. Canine and feline malignant mammary tumors are fairly common in middle-aged animals and have a metastatic pattern similar to that in women; that is, primarily to regional lymph nodes and lungs. Chemotherapy has been minimally effective, and these tumors may be better models for testing biological response modifiers. Oral tumors, especially melanomas, are the most common canine malignant tumor in the oral cavity. Metastasis is frequent, and the response to chemotherapy and radiation has been disappointing. This tumor can be treated with anti-metastatic approaches or biological response modifiers. Squamous cell carcinomas, especially in the gum, are excellent models for radiation therapy studies. Nasal carcinomas are commonly treated with radiation therapy. They tend to metastasize slowly, but have a high local recurrence rate. This tumor is suitable for studying radiation therapy approaches. Primary lung tumors and soft tissue sarcomas are excellent models for studying combined modality therapy such as surgery with chemotherapy or biological response modifiers. Finally, non-Hodgkin's lymphoma is a common neoplastic process seen in the dog. These tumors respond to combination chemotherapy and have great potential as a model for newer chemotherapeutic agents and biological response modifiers. This paper will further elaborate on the relative merits of each tumor type as a model for human cancer therapy and biology.

Animals↗

Metastatic behavior of prostate cancer. Cluster analysis of patterns with respect to estrogen treatment.

The responsiveness of prostate cancer to treatment with estrogen has been recognized for over 40 years, but whether the effect is mediated by diminished tumor growth or reduction in metastatic spread is not known. To answer this question the authors reviewed the clinical and pathologic features of 89 patients with metastatic prostate cancer after autopsy. Sixty-three percent of the patients studied were black. Patients treated with estrogen survived somewhat longer (0.05 less than P less than 0.10), but they had significantly greater numbers of metastatic sites (P less than 0.001) and greater overall tumor burden (P less than 0.001), with significantly increased frequencies of metastases to the liver, adrenal gland, bone, lymph nodes, large bowel, lungs, serosal surfaces, ureters, and central nervous system (CNS) (all P less than 0.05 or lower) compared with patients who had not been treated with estrogen. However, patients not treated with estrogen more frequently died from other causes (P less than 0.001). When the patients who died from other causes were excluded from the data analysis, there were no significant differences in the number of metastatic sites between patients who received estrogen therapy and those who did not, and the only remaining significant difference in the distribution of metastases was that patients who received estrogen treatment had more frequent metastases to the adrenal cortex and CNS (P less than 0.05). These observations were corroborated by cluster analysis of the metastatic patterns. Cluster analysis also identified a subset of predominantly (67%) black patients who developed distant metastases without much local spread of tumor. This suggests that tumor behavior in this group was less predictable than for the other patients in whom disease appeared to progress from Stage A to Stage D as expected. The authors conclude that estrogen therapy may prolong survival by slowing the rate of tumor growth rather than by inhibiting the metastatic progression of prostate cancer or destroying selective populations of tumor cells.

Adenocarcinoma↗

Attachment of neuroblastoma cells to extracellular matrix: correlation with metastatic capacity.

Extracellular matrix (ECM) serves important attachment functions during organogenesis in mammalian species. When layered on a plastic surface, ECM extracted from the rat lung, liver, or kidney enhances the attachment of C1300 murine neuroblastoma cells to that surface. Enhanced attachment to ECM by these cells correlates with their potential to form metastatic deposits in vivo. Conversely, neuroblastoma cells selected for increased metastatic potential by in vivo passaging demonstrate enhanced attachment to organ-derived ECM. However, although ECM provides attachment sites for these murine neuroblastoma cells, the attachment is not preferential for any of the organ ECMs tested (lung, liver, kidney). Histopathologic examination of the murine liver, lungs, and kidneys performed 20 to 22 days after intravenous inoculation of C1300 cells reveals notable metastatic seeding in each of these organs, but the liver clearly exhibits a greater degree of replacement by tumor metastases than the lungs or the kidneys. Therefore, the data from the attachment assays, coupled with the histopathologic findings obtained after tumor inoculation, suggest that although the ability to attach to ECM correlates with metastatic potential, additional factors are important in determining the preferential pattern of metastatic disease observed in murine neuroblastoma.

Animals↗

Regression of metastatic liver tumors in rats treated with angiogenesis inhibitor TNP-470: occurrence of apoptosis and necrosis.

To clarify the mechanism of the reduction of metastatic liver tumors in rats treated with angiogenesis inhibitor TNP-470, the death of tumor cells was examined pathologically and ultrastructurally. Liver metastases were developed by intravenous injection of AH-130 cells. TNP-470 was given subcutaneously after tumor cell injection. Alterations in the size and number of metastatic tumors were examined at various time points, in association with the analysis of cell death pattern. The metastatic nodules were divided into 4 groups according to the morphological patterns of cell death; no cell death, scattered apoptosis, central necrosis, and diffuse necrosis. The number and size of the metastatic tumors at 2 weeks in untreated rats were larger than those in treated rats. The number of tumors in untreated rats decreased, but the tumor size increased. All rats treated with TNP-470 were alive and free from tumors after 4 weeks, whereas all the untreated rats died of liver metastases. The percentages of the tumors with necrosis in untreated rats (61.2% at 2 weeks and 100% at 4 weeks) were significantly higher than that (31.8% at 2 weeks) in treated rats (P < 0.01). The percentage of the tumors containing apoptotic cells in treated rats was significantly higher than that in untreated rats (54.5% vs. 30.6%; P < 0.05). The growth of metastatic tumors without treatment might be faster than the growth of vessels in untreated tumors, resulting in central necrosis due to ischemia. On the other hand, the reduction of metastatic liver tumors treated with TNP-470 might be caused by inhibition of angiogenesis, providing a weak ischemic stimulus which triggers apoptosis, rather than by a direct cytotoxic effect on tumor cells, because previous in vivo experiments demonstrated that TNP-470 affected endothelial cells but not tumor cells.

Animals↗