Carcinoid tumor metastatic to the breast

Breast metastases from nonmammary malignant neoplasms are uncommon, accounting for approximately 2% of breast tumors. There are 13 cases reported in the literature of carcinoid tumor metastatic to the breast, and more than half of these cases were misdiagnosed pathologically and treated as primary breast carcinoma, even in cases with a medical record of carcinoid tumor. We describe a patient with a history of asthma and diarrhea who presented to the University of Arkansas for Medical Sciences, Little Rock, with an exacerbation of the asthma. The results of routine physical examination revealed a mass in the left breast. A diagnosis of carcinoid tumor metastatic to the breast was made after a partial mastectomy was performed. The differential diagnosis between primary carcinoid tumor of the breast and carcinoid tumor metastatic to the breast is often controversial in surgical pathology. Diagnoses need to be made correlating clinical and histological examination in difficult cases in which there is not a diagnosis of carcinoid tumor elsewhere. Accurate diagnosis of breast metastases is important to avoid unnecessary treatment.     

Bronchial carcinoid tumor metastatic to the breast

We report a case of bronchial carcinoid that initially manifested as metastatic tumor in the breast. An exhaustive search for the primary tumor yielded the finding of a large right lung mass. Subsequent histopathologic examination of the resected lung and breast tissues confirmed the lung cancer as a primary tumor and the breast tumor as metastatic disease.     

Phyllodes tumour in pregnancy: a case report

An 18 1/2-year-old castrated male donkey with progressively worsening right forelimb lameness presented with a mass on the distal dorsal aspect of its P3 bone. Grossly, the firm, gritty mass was infiltrative, disrupted the contours of the overlying hoof wall, and had mottled and cavitated areas on cut surface. Histologically, the growth was composed of densely cellular sheets of mildly pleomorphic mesenchymal cells forming irregularly shaped islands of poorly mineralized osteoid. The neoplastic mass had patchy areas of necrosis. The diagnostic possibilities considered for this donkey's mass include osteosarcoma, osteoma, ossifying fibroma, and fibrous dysplasia. Careful consideration of the gross and histological characteristics of this donkey's mass support a diagnosis of osteosarcoma.     

Increased hyaluronidase levels in breast tumor metastases

We summarize the recommendations for research that emerged from a NIMH-sponsored Conference on HIV, AIDS, and Severe Mental Illness. Recommendations are made in four areas, namely, epidemiology of HIV infection, epidemiology of sexual and drug-use risk behaviors, risk reduction and transmission prevention, and treatment of infected persons. This research is urgently needed to adequately respond to the AIDS epidemic among people with severe mental illness.     

Rare differential diagnosis of breast tumor. Giant cell tumor of the ribs

We report a case of a breast tumor. As carcinoma of the breast was suspected, a biopsy was taken and a very rare osteoclastoma originating in the rib was identified. Semimalignant bone tumors tend to recur locally. The symptoms are nonspecific; the initial diagnosis is often made late. To differentiate the diagnosis, one should think about primary and secondary bone diseases and tumors of the organs of the thorax. In our case, the tumor was completely resected, including the ribs, and the defect was covered with a corium plasty. In this way, we are able to save the breast. We discuss different methods for covering chest wall defects.     

Carcinoma-associated retinopathy in breast carcinoma and carcinoid tumor

Mice maintained on a low protein diet for 30 days and then infected with Schistosoma mansoni for 16 weeks completely failed to develop 'pipestem fibrosis' of the liver, whereas 50% of well nourished controls did. Usually mice with relatively mild and prolonged S. mansoni infection develop two different pathological pictures: one consisting of disseminated portal fibrosis caused by periovular granulomas concentrated at the portal spaces (pipestem fibrosis), the other represented by scattered hepatic granulomas. The reason for this dual response is poorly understood. Combined results from parasitological, histopathological, biochemical and morphometric data revealed that peri-ovular granulomas of undernourished mice were smaller, inflammation was less intense and there was minimal fibrosis in comparison with those of controls, which suggest that a vigorous host response is necessary for the pathogenesis of schistosomal portal fibrosis.     

FDG PET evaluation of granular cell tumor of the breast

Granular cell tumor is a rare, usually benign neoplasm of neural origin that may arise in virtually any site and, when situated in the breast, can mimic breast carcinoma. We describe a case of granular cell tumor of the breast in a 57-yr-old woman. Clinical evaluation, mammography, sonography and MRI suggested a carcinoma with infiltration of skin and muscle. However, the tumor did not display increased glucose metabolism on PET. Clinical findings, imaging results, histological characteristics and surgical management are discussed.     

Primary malignant tumor of the breast. Monitoring after treatment

The appropriate follow-up of primary breast cancer patients is a controversial topic: an intensive surveillance is the rule for many oncologists, but the beneficial effect of this attitude has never been demonstrated. Two consensus conferences focused on this issue, both discouraged the routine use of laboratory tests, chest X-ray, radionuclide bone scan or liver echography which involve a high financial cost. For these routine investigations the sensitivity to detect recurrence is less than 5%. History and physical examination remain the best methods to detect a recurrence, and mammogram is helpful for detecting recurrent disease in the treated breast or a new primary cancer in the controlateral breast, which both are curable. The purpose of intensive follow-up is earlier detection of recurrence in order to treat as early as possible, but two randomized studies failed to demonstrate a survival benefit in 2600 patients. However with current treatments, only a follow-up study including a very large number of patients could detect a survival difference. The demonstration of an intensive follow-up benefit is similar in screening studies where it is recommended to use the most predictive, the less toxic and the less expensive test. Serum C.A. 15.3 level which best anticipates diagnosis in follow-up is one of the best candidates to be used in a randomized study.     

Immunohistochemical detection of tumor cells in the bone marrow of breast cancer patients

BACKGROUND: Contamination of bone marrow and peripheral blood stem cells with tumor cells is a problem that may be encountered when autologous hematopoietic stem cell transplantation is conducted concurrently with high-dose chemotherapy. METHODS: Using monoclonal antibodies to a variety of tumors, the detection of tumor cells in the bone marrow of breast cancer patients was studied by immunohistochemistry. RESULTS: KL-1 and CAM5.2 were strongly reactive with breast cancer cells, but not with normal bone marrow cells. The reactivity of the tumor cells with EMA was not strong, and DF-3 and 115D8 yielded only slightly positive reactions. These latter antibodies also exhibited some reactivity to normal bone marrow cells. When tumor cells were admixed with normal cells, the sensitivity of CAM5.2 and EMA permitted the detection of one cell in 10(4), but with KL-1, the detection of one in 10(5) cells was possible. When immunohistochemical staining was used in testing 40 patients with advanced or recurrent breast cancer, positive reactions were obtained in four of 27 patients (14.8%) with KL-1, four of 26 (15.4%) with CAM5.2, and nine of 37 (23.7%) with KL-1 + CAM5.2, figures similar to those reported by others who studied stage IV patients. CONCLUSIONS: Immunohistochemical staining with KL-1 and CAM5.2 is therefore considered to be a useful technique for detecting contamination by tumor cells.     

Defective acidification in human breast tumor cells and implications for chemotherapy

Multidrug resistance (MDR) is a significant problem in the treatment of cancer. Chemotherapeutic drugs distribute through the cyto- and nucleoplasm of drug-sensitive cells but are excluded from the nucleus in drug-resistant cells, concentrating in cytoplasmic organelles. Weak base chemotherapeutic drugs (e.g., anthracyclines and vinca alkaloids) should concentrate in acidic organelles. This report presents a quantification of the pH for identified compartments of the MCF-7 human breast tumor cell line and demonstrates that (a) the chemotherapeutic Adriamycin concentrates in acidified organelles of drug-resistant but not drug-sensitive cells; (b) the lysosomes and recycling endosomes are not acidified in drug-sensitive cells; (c) the cytosol of drug-sensitive cells is 0.4 pH units more acidic than the cytosol of resistant cells; and (d) disrupting the acidification of the organelles of resistant cells with monensin, bafilomycin A1, or concanamycin A is sufficient to change the Adriamycin distribution to that found in drug-sensitive cells, rendering the cell vulnerable once again to chemotherapy. These results suggest that acidification of organelles is causally related to drug resistance and is consistent with the hypothesis that sequestration of drugs in acidic organelles and subsequent extrusion from the cell through the secretory pathways contribute to chemotherapeutic resistance.     

Relationship between matrix metalloproteinase expression and tumor angiogenesis in human breast carcinoma

Intratumoral proteases are known to be involved in not only tumor cell invasion but also a variety of stromal reactions including neovascularization. In this study, we have examined the expression of matrix metalloproteinases (MMPs) by gelatin gel zymography and compared its expression with angiogenesis activities including the expression of several endothelial growth regulators and intratumoral microvessel density (MVD) in human breast cancer tissues. There was a significant correlation between activated MMP-2 expression and vascular endothelial growth factor (VEGF) expression (p=0.045). In addition, the expression of activated MMP-9 expression was significantly correlated with thymidine phosphorylase (TP) expression (p=0.0044). Pro MMP-9 expression tended to correlated with the increment of MVD (p=0.063). MMP-2 and MMP-9 expressions were frequently co-upregulated with endothelial growth regulators in human breast cancer tissues, which underlines the cooperative function of MMPs in neovascularization.     

Use of serum tumor markers for the diagnosis and follow-up of breast cancer

Human immunodeficiency virus (HIV) seroprevalence rates among rural trauma patients range between 0.15 and 1.32 per cent. A random sample of trauma patients treated at our rural trauma center between September 1994 and November 1995 was enrolled into a blind HIV serosurvey. Five hundred sixty-six of 1315 trauma patients (43%) were tested. Two of the 566 patients (0.35%) were HIV positive. A review of aggregate data for HIV infection among rural trauma patients in the United States show that 28 of the 4639 patients (0.60%) are HIV positive. We conclude that there was a low HIV incidence among our trauma patients from September 1994 to November 1995, and the cost-effectiveness of HIV testing for rural trauma patients is questionable with incidences between 0.5 and 1.0 per cent.     

Malignant phyllodes tumor of the breast with hypoglycemia: report of a case

A surgically resected case of giant malignant phyllodes tumor of the breast associated with a hypoglycemic attack is reported. A 54-year-old woman was referred to our hospital with loss of consciousness and a huge chest wall tumor. She was diagnosed as having a malignant phyllodes tumor by core needle biopsy and underwent palliative simple mastectomy because lung metastasis was detected on computed tomography and by other imaging modalities on admission. The preoperative laboratory data revealed a very low fasting blood sugar level of 37 mg/dl. After removal of the tumor, the blood sugar level gradually normalized (90-100 mg/dl) and the plasma insulin-like growth factor-II (IGF-II) level promptly decreased. The IGF-II level of tumor extracts was high (2500 ng/g wet weight) and the majority of atypical cells stained positively for IGF-II immunohistochemically. These findings suggested that the patient's hypoglycemia was associated with IGF-II produced by a giant malignant phyllodes tumor that consumed glucose.     

Solitary breast metastasis as first manifestation of ovarian carcinoid tumor

Carcinoid tumor metastatic to the breast is very uncommon. The rarity of this finding may be the reason for its common misinterpretation as primary breast carcinoma. A patient with primary ovarian carcinoid that presented initially with a solitary breast mass is reported. A review of the literature discloses only 12 reported cases of carcinoid tumor metastatic to the breast, with none of the primaries found to be the ovary.     

Markov models of breast tumor progression: some age-specific results

Researchers have noted that mammographic screening has a reduced effect on breast cancer mortality in women in their forties compared to older women. Explanations for this include poorer sensitivity in younger women due to denser breast tissue, as well as more rapid tumor progression, giving a shorter mean sojourn time (the average duration of the preclinical screen-detectable period). To test these hypotheses, we developed a series of Markov-chain models to estimate tumor progression rates and sensitivity. Parameters were estimated using tumor data from the Swedish two-county trial of mammographic screening for breast cancer. The mean sojourn time was shorter in women aged 40-49 compared to women aged 50-59 and 60-69 (2.44, 3.70, and 4.17 years, respectively). Sensitivity was lower in the 40-49 age group compared to the two older groups (83%, 100%, and 100%, respectively). Thus, both rapid progression and poorer sensitivity are associated with the 40-49 age group. We also modeled tumor size, node status, and malignancy grade together with subsequent breast cancer mortality and found that, to achieve a reduction in mortality commensurate with that in women over 50, the interscreening interval for women in their forties should be less than two years. We conclude that Markov models and the use of tumor size, node status, and malignancy grade as surrogates for mortality can be useful in design and analysis of future studies of breast cancer screening.     

Dietary fat and breast cancer metastasis by human tumor xenografts

Human breast cancer cell lines growing as xenografts in athymic nude mice have been used to examine the effects of dietary fat and fatty acids on tumor progression. The estrogen independent MDA-MB-435 cell line has the advantage that it metastasizes consistently to the lungs and forms quantifiable secondary nodules when injected into the mammary fat pads. With these breast cancer cells, the stimulating effects of polyunsaturated omega-6 fatty acids on both primary tumor growth and metastasis were demonstrated; in contrast, the long-chain omega-3 fatty acids were inhibitory. The model can also be adapted to examine dietary fatty acids, and inhibitors of their metabolism, as experimental adjuvant therapy after surgical excision of the primary tumors. Unfortunately, estrogen dependent human breast cancer cells do not metastasize, or do so rarely, in nude mice; in consequence, it is not possible to use the model to study estrogen-fatty acid interactions on the metastatic process. In addition to metastasis from a primary location, intravenous injection of MDA-MB-435 cells into the nude mouse host, particularly when combined with studies using Matrigel-based in vitro invasion assays, permits further dissection of the steps in the metastatic cascade which are influenced by dietary fatty acids. The results obtained by these several approaches have demonstrated distinct roles for the cyclooxygenase and lipoxygenase-mediated products of omega-6 fatty acid metabolism, and suggest new approaches to experimental breast cancer therapy.     

Relationship of variations in tumor cell kinetics induced by primary chemotherapy to tumor regression and prognosis in locally advanced breast cancer

We have studied binding of isradipine to A7r5 vascular smooth muscle cells as a function of membrane potential and cell proliferation. Consistent with a voltage-modulated receptor model, two classes of binding sites were detected in confluent cultures: high-affinity sites under depolarizing (50 mM K+) conditions (Kd = 45 +/- 3 pM), and lower affinity sites under resting (5 mM K+) conditions (Kd = 181 +/- 20 pM). However, proliferating cells also displayed the high-affinity state at rest (Kd = 29 +/- 9 pM) in addition to a low-affinity site (Kd = 869 +/- 383 pM). Analysis of dissociation rates also revealed two receptor classes during proliferation. Proliferating cells showed a single class of high-affinity sites (Kd = 39 +/- 6 pM) when depolarized, similar to confluent cells. Receptor density in confluent monolayers increased from 15 +/- 3 fmol/10(6) cells at 5 days to 72 +/- 6 fmol/10(6) cells after 10 days. These results suggest (i) that some L-type Ca2+ channels are spontaneously active in proliferating vascular smooth muscle cells, but require depolarization to activate in a confluent monolayer, and (ii) that the density of dihydropyridine receptors increases after a monolayer becomes confluent.