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PubMed1999

[Multiple stress fractures of the anterior and posterior pelvic ring with progressive instability. Description of a pronounced case with review of the literature].

We report a case of a 64-year old female patient, who developed a total instability of the pelvic ring within one year as a result of increasing insufficiency fractures. A minor trauma of the pelvis was assumed to be the trigger of this process retrospectively. The radiographic appearance of the multiple pseudoarthrosis simulated a metastatic disease. The differential diagnosis and the typical pattern of sacral insufficiency fractures (SIF) are described.

Bone Transplantation↗

PubMed1985

Immunologic patterns of regional lymph nodes in squamous cell carcinoma of the floor of the mouth. Prognostic significance.

Histologic specimens from 43 patients with squamous cell carcinoma of the floor of the mouth treated exclusively by surgery were studied with special attention paid to the reactivity of regional lymph nodes. The lymph nodes were classified into four microscopic patterns of immune response: lymphocyte predominance for sinus histiocytosis, germinal center predominance, unstimulated, and lymphocyte depletion. No nodes of the lymphocyte depletion pattern were found. Correlations were then made between the patterns and survival rate at 5 year follow-up. The results showed that those patients with lymph nodes that demonstrated lymphocyte predominance had a better survival rate than patients with germinal center predominance and the unstimulated patterns. These correlations were independent of stage and metastatic nodal status and the differences were statistically significant (p less than 0.5). Morphologic assessment of immunologic activity in lymph nodes that drain carcinoma of the floor of the mouth appears to be of significant prognostic value.

Adult↗

PubMed1981

Urinary excretion levels of unconjugated pterins in cancer patients and normal individuals.

Urinary excretion levels of seven unconjugated pterins in healthy individuals and in cancer patients, most of whom were undergoing chemotherapy, were measured utilizing a newly developed high-pressure liquid chromatographic system. Excretion of pterins in the control group appears to be under strict metabolic control as the values obtained were confined within a small range. When the mean excretion levels in control subjects were compared with those in cancer patients, we found a significant increase in the excretion of xanthopterin, neopterin and pterin and a significant decrease in isoxanthopterin by cancer patients. Biopterin levels, on the other hand, were found only slightly but not significantly increased, whereas pterin-6-carboxylic acid and 6-hydroxymethylpterin were found to be excreted in approximately equal amounts in both groups. Urinary excretion levels of pterins were monitored for a period of nine months in a patient being treated with chemotherapy for metastatic ovarian carcinomatosis. We found that the excretion pattern of pterins appeared to correlate with the clinical status of the patient. These results indicate that a definite imbalance in pterin, and possibly folate metabolism, is associated with the presence of malignant diseases.

Adult↗

PubMed2006

Investigations for bone metastasis from an unknown primary.

OBJECTIVES: To evaluate the respective contributions of various investigations used to identify the primary tumor in a cohort of patients referred for diagnostic evaluation of one or more bone metastases. METHODS: A single-center retrospective study was conducted in a cohort of patients admitted between October 1990 and January 2000 for evaluation of one or more bone metastases with no known primary. All patients underwent radionuclide bone scanning, a chest radiograph, and an abdominal ultrasound scan. Computed tomography (CT) of the chest and abdomen, CT of the brain, and tumor marker assays were performed as clinically indicated. Using the final diagnosis as the reference standard, we evaluated the diagnostic usefulness of each investigation. RESULTS: The 152 patients (104 men and 48 women) had a mean age of 63.5+/-12.5 years. The primary was located in the lung in 37 patients, prostate in 26, breast or female genital tract in 24, urinary system in 11, gastrointestinal tract in 11, head and neck in 6, and other organs in 4. In 33 patients, no primary was identified. The extraskeletal metastases were located chiefly in the liver (20.4%), lung (17.1%), pleura (13.2%), and brain (7.2%). Bone biopsies were performed in 107 patients: 84 had a single bone biopsy, 16 had two bone biopsies, and 7 had three bone biopsies. The first bone biopsy was taken in the rheumatology department with or without fluoroscopic guidance in 62 patients, in the radiology department under CT guidance in 6 patients, and in the surgery department in 32 patients; this information was unavailable for the 7 remaining patients. The first bone biopsy was taken from the iliac bone in 48 patients, spine in 32, sacrum in 10, rib in 3, and other sites in 7. The histological biopsy findings indicated adenocarcinoma in 58 cases, epidermoid carcinoma in 28 cases, undifferentiated carcinoma in 2 cases, and other histological patterns in 9 cases. In 80 patients, another metastatic site was easier to access than the bone metastasis. Tumor marker assays were of limited value for determining the site of the primary, with the exception of prostate-specific antigen. CONCLUSION: Bone biopsies performed by rheumatologists, generally under fluoroscopic guidance, usually indicate the site of the primary or at least the histological type. Tumor markers are often positive but are of limited usefulness for identifying the primary.

Adenocarcinoma↗

PubMed1999

Infiltrative subcutaneous malignant fibrous histiocytoma: a comparative study with deep malignant fibrous histiocytoma and an observation of biologic behavior.

Malignant fibrous histiocytoma (MFH) is one of the most common soft tissue sarcomas of adulthood. Although it is usually intramuscular and pseudocapsulated, we have recently observed MFHs with extremely infiltrative growth margins, which are predominantly located in the subcutis. These lesions are often associated with incomplete primary surgical excision, the subsequent need for additional surgery or adjuvant therapy, and an increased risk for local recurrence. To further analyze the growth pattern and clinical implication of the subcutaneous infiltrative MFHs, we reviewed a series of 24 subcutis and 21 intramuscular MFHs of the extremities. Morphologically, we defined "infiltrative" as tumor extension along normal tissue planes for a minimum measurable distance of 2 mm from the edge of the main mass. Radiographic findings were correlated with pathologic findings. Of the 24 subcutis MFHs, 83% showed an infiltrative growth pattern, involving 5% to 90% (mean, 51%) of the evaluable margin. Fifty percent of patients with subcutaneous MFH had both an infiltrative growth pattern and positive surgical resection margin on initial resection. Only 25% noninfiltrative subcutaneous MFHs had a positive initial surgical resection margin. Of the 21 intramuscular MFHs, only 5 (24%) had an infiltrative growth pattern that involved 5% to 90% (mean, 40%) of the evaluable margin. One of the five tumors had 90% margin infiltration with multiple positive surgical resection margins. Of 16 noninfiltrative intramuscular MFHs, 3 (19%) had positive resection margins. Magnetic resonance imaging (MRI) and/or computed tomography (CT) scan correctly identified the growth pattern in 87% of subcutaneous and 88% of intramuscular MFHs. Patient follow-up evaluation showed that four (17%) patients with subcutaneous MFHs had resection-proven recurrences, 6 to 57 months after diagnosis. All four of these tumors had infiltrative growth patterns and positive margins on the original surgical resection. There were no local recurrences of the intramuscular MFHs. Two patients of 20 in the infiltrative subcutaneous MFH group and two patients of four in the well-circumscribed subcutaneous MFH group had biopsy-proven metastases, which developed within 5 years after diagnosis. Six patients had metastases in the intramuscular MFH group. A group of MFHs, predominantly subcutaneous, have an extremely infiltrative growth pattern. This growth pattern, documented by radiographic methods and/or light microscopic examination of biopsy specimens, should indicate that a wider margin on initial resection is necessary to entirely excise the lesion. The presence or absence of an infiltrative growth pattern is not predictive of the tumor's metastatic potential.

Adult↗

PubMed2006

Role of TTF-1, CK20, and CK7 immunohistochemistry for diagnosis of primary and secondary lung adenocarcinoma.

Thyroid transcription factor-1 (TTF-1), and cytokeratin 7 (CK7) and cytokeratin 20 (CK20) have recently been reported to be useful to distinguish between primary and metastatic lung adenocarcinoma. The aim of this study was to determine the usefulness of the staining patterns of pulmonary adenocarcinoma with antibodies to TTF-1, CK7, and CK20 in differentiating primary from metastatic pulmonary adenocarcinoma. Of the 66 lung adenocarcinoma specimens that were enrolled in our study, there were 40 primary lung adenocarcinomas, 12 metastatic adenocarcinomas from breast, 13 metastatic adenocarcinomas from colon, and 1 metastatic adenocarcinoma from stomach. The expression of TTF-1, CK7, and CK20 was assessed by immunohistochemistry. We found that 73% of primary lung adenocarcinomas expressed TTF-1, whereas all nonpulmonary adenocarcinomas lacked TTF-1 staining. CK7 expression was significantly more frequent in adenocarcinomas of pulmonary and breast origin than gastrointestinal (GI) origin (p < 0.001). In contrast, CK20 expression was significantly more prevalent in adenocarcinoma that originated in the GI tract than that of pulmonary or breast origin (p < 0.001). A combination of TTF-1+CK7+CK20- was highly significantly associated with primary adenocarcinoma of lung (vs GI tract, p < 0.001; vs breast, p < 0.001). A combination of TTF-1-CKCK20+ was highly significantly associated with adenocarcinoma of GI origin (vs lung, p < 0.001; vs breast, p < 0.001). Our study has confirmed that expression of CK7, CK20, and TTF-1 is a useful immunohistochemical marker for diagnosis of lung tumors and for differential diagnosis of primary pulmonary adenocarcinomas from extrapulmonary adenocarcinomas metastatic to the lung. Application of this panel of antibodies might be expected to increase the accuracy of diagnosis.

Adenocarcinoma↗

PubMed1985

Immunocytochemical demonstration of p21 ras family oncogene product in normal mucosa and in premalignant and malignant tumours of the colorectum.

Study of the distribution of the p21 ras oncogene product as demonstrated by monoclonal antibody Y13-259 shows this protein to be apparently present in all epithelial populations of both premalignant and malignant tumours and throughout the normal foetal and adult epithelial crypt population in the colorectum. Metastatic tumour in liver shows a similar staining pattern which is less intense however than in the surrounding normal hepatocytes. Our results suggest that the presence of this protein is a widespread feature of normal cellular metabolism in certain cell types and is not restricted to those actively involved in cellular proliferation. It appears, furthermore, that neither cells at different stages of carcinogenesis nor those representing variants of a malignant phenotype can be identified using this particular antibody.

Antibodies, Monoclonal↗

PubMed1989

Phase II study of lonidamine in metastatic breast cancer.

Thirty patients with previously treated metastatic breast cancer were entered in a phase II study with oral lonidamine. Twenty-eight patients are evaluable for toxicity and 25 for response. A partial remission was obtained in four patients (16%) and disease stability in 11 (44%): 10 patients progressed (40%). Toxicity was acceptable, consisting mainly of myalgias (39% of patients) and asthenia (21.4%). No myelotoxicity was observed. The drug is active in previously treated metastatic breast cancer and, because of its peculiar pattern of action and toxicity, deserves to be evaluated in combination with cytotoxic chemotherapy.

Adult↗

PubMed1994

TP53 allele loss, mutations and expression in malignant melanoma.

p53 alterations at the DNA, mRNA and protein levels were studied in tumour metastases sampled from 30 patients with malignant melanoma. Paraffin-embedded sections from these and an additional 12 patients were examined for the presence of p53 protein. TP53 gene aberrations were found in 7 of 30 (23%) of the patients, six of which showed loss of heterozygosity (LOH). Point mutations were detected in only two cases, one of which had LOH whereas the other was non-informative. Increased levels of p53 mRNA were present in only one tumour with, but in six cases without, detectable DNA abnormalities. Four of the latter and six tumours with normal transcript levels had immunohistochemically detectable levels of p53 protein. In 25 cases in which corresponding primary and metastatic lesions could be compared, closely similar immunoreactivity patterns were observed. Increased expression of the MDM2 gene was found in only one tumour in parallel with overexpression of p53. Altogether, the data indicate that inactivation of the p53 regulatory pathway is not of major significance in the tumorigenesis of malignant melanoma. However, a significant association was found between p53 immunoreactivity and the relapse-free period in patients with superficial spreading melanoma. That increased protein expression was predominantly found in tumours without DNA alterations might suggest a role for the wild-type p53 protein in restricting malignant cell proliferation in these cases.

Alleles↗

PubMed1981

Diagnosis of carcinoid-like metastatic prostatic carcinoma by an immunoperoxidase method.

An unusual case of carcinoma of the prostate with metastases is described. the prostate and the metastases showed adenocarcinoma with carcinoid-like areas. A tumor with the same histologic features was found at the tip of the appendix and proved to be metastatic. The possibility of primary carcinoid of the prostate was considered; however, Fontana-Masson stain and electron microscopy failed to confirm this. Immunoperoxidase stain for prostatic acid phosphatase was done on the prostate and metastases. This stain is specific for tissues of prostatic origin. The stain was positive in the carcinoid-like areas, indicating that it was not a true carcinoid but rather prostatic carcinoma with a carcinoid-like pattern. Apparently, this is the first case of a metastatic prostatic carcinoma showing carcinoid-like areas that were positive for prostatic acid phosphatase.

Acid Phosphatase↗

PubMed1984

Computed tomography of spontaneous osteoporotic sacral fractures.

Spontaneous osteoporotic sacral fractures are an uncommon entity. They are difficult to image on plain films. Clinically, they may be confused with metastatic disease. A peculiar H-shaped uptake pattern on bone scan should suggest the condition, and CT can then demonstrate the fracture. In this case this combination of radionuclide scan and CT permitted differentiation of a sacral fracture from presumed bony metastases.

Diagnosis, Differential↗

PubMed2001

Mechanisms governing bone metastasis in prostate cancer.

Why does prostate cancer metastasize to bone? Why is there increased turnover of the bone matrix in the presence of prostate cancer? A recent autopsy study supports a traditional hypothesis that gross, anatomic patterns of blood flow influence the distribution of metastatic deposits. On the other hand, recent developments in animal models of prostate cancer bone metastasis have renewed interest in the traditional 'seed and soil' hypothesis: several studies point to specific biological interactions between prostate cancer cells and the bone microenvironment that can explain the tendency of prostate cancer cells to colonize bone and grow into clinically relevant metastatic deposits. Some studies implicate mechanisms including chemoattraction and enhanced adherence to bone endothelium. Additional data suggest that prostate cancer cells are 'osteomimetic', that is, they take on the properties and behaviors of osteoblasts or osteoclasts upon arrival in bone. These activities lead to enhanced turnover of the bone matrix and may explain the propensity of prostate cancer to grow in bone. Finally, a series of studies have implicated other molecular markers as distinguishing characteristics of bone-metastatic prostate cancer tissue.

Animals↗

PubMed2003

erbB-2 (HER-2) and breast cancer progression.

The purpose of this study was to explore differences in erbB-2 alterations in recurrent or metastatic disease, as compared with the primary tumor. Primary invasive breast cancers and subsequent local, regional, or distant metastases from 113 patients were examined. Primary and all metastatic or recurrent tumors were evaluated for erbB-2 expression using immunohistochemistry (with CB11, TAB 250, DAKO anti-erbB-2, HercepTest) and fluorescence in situ hybridization. Immunohistochemical data derived from the 4 reagents on the same tumor sample were highly correlated (pair-wise correlation range, 78-90%). Immunohistochemical and fluorescence in situ hybridization erbB-2 data were also generally concordant (average agreement, 82%; range, 75-87%). Approximately 80% of the primary and recurrent or metastatic tissues from the same patient had similar patterns of erbB-2 protein expression and gene copy number, although in approximately 20%, disagreement was observed. Discordant cases were mostly erbB-2 normal primary tumors with altered metastases, although the opposite pattern was also observed. Interestingly, erbB-2 discordance, based on CB11 data, was associated with subsequent survival, whereas there were no similar associations with other erbB-2 stains. In approximately 80% of patients, erbB-2 protein expression and gene copy number were similar in the primary tumor and locally recurrent or distant metastases. The lack of complete concordance suggests clonal selection or genetic drift in some cases.

Breast Neoplasms↗

PubMed1979

Scintigraphy and ultrasonograhy of hepatic hemangioma.

The clinical findings, radionuclide scintigrams, and ultrasonograms of hepatic hemangiomas are described for 11 patients. Scintigraphy frequently demonstrated a marginal or subcapsular location. The lesions were otherwise nonspecific in appearance and were indistinguishable from metastatic foci. Sonographically, hypoechoic, hyperechoic, and predominantly anechoic patterns were observed, not unlike those described for malignant foci. However, 7 hemangiomas had a central linear septum. Liver function tests were normal in all patients. Since percutaneous biopsy is hazardous and hepatic angiography usually diagnostic, the scintigraphic and ultrasonic appearances described may help in the selection of the appropriate investigative studies.

Hemangioma↗

PubMed2006

Behavioral profiling of human transitional cell carcinoma ex vivo.

Outcome studies of many types of cancer have revealed that tumors of indistinguishable histologic appearance may differ significantly in aggressiveness and in their response to therapy. A strategy that would enable early identification of patients at high risk for disease progression and allow screening of multiple therapeutic agents simultaneously for efficacy would improve clinical management. We have developed an orthotopic organ culture model of bladder cancer in which quantum dot-based fluorescent imaging approaches are used to obtain quantitative measurements of tumor cell behavior. Human transitional cell carcinoma (TCC) cells are labeled with quantum dot nanoparticles, and the cells instilled into the rat bladder in vivo, after which the bladder is excised and cultured ex vivo. Cell implantation, proliferation, and invasion into the organ wall are monitored using epifluorescence imaging and two-photon laser scanning confocal microscopy. Using this approach, we were able to assign distinct phenotypes to two metastatic bladder cancer cell lines based on different patterns of invasiveness into the bladder wall. We also showed that established tumor cell masses regressed following intravesical administration of the chemotherapeutic drug thiotepa. Collectively, these findings suggest that this assay system, which we have named EViTAS (for ex vivo tumor assay system), can recapitulate salient aspects of tumor growth in the host and is amenable to behavioral profiling of human cancer.

Animals↗

PubMed1981

[Computerized tomography of supratentorial meningiomas: results in 32 cases].

Thirty two cases of supratentorial meningiomas diagnosed by computerized tomography and surgically proved are reported. The authors did not included in this series meningiomas of the orbit. The higher frequency is observed in the convexity area (eleven cases), followed by the sphenoidal ridge area (nine cases). There is a predominance in the females (65.6%) over the males (34.3%). The age varies from fourteen to seventy eight and only three patients are below thirties. Homogeneous contrast enhancement of all tumours was obtained by injecting a bolus of 75ml of Vasconray (30g of total iodine per patient) or 80ml of Hypaque 75 (30.8g of iodine). None of them showed the ring pattern observed in cases of abscess, gliomas or metastatic lesions. The edema seen around the tumours tended to be minimal, unless in those tumours located in the frontal region where the mass effect tended to be more pronounced. Hydrocephaly was observed in three cases.

Adolescent↗

PubMed2002

Adult rhabdoid renal cell carcinoma.

BACKGROUND: Pediatric rhabdoid tumor of the kidney is regarded as a distinct neoplasm, whereas rhabdoid differentiation in adult renal cell carcinoma is usually found in association with conventional (clear cell) tumor, from which it is thought to evolve. OBJECTIVE: To further characterize the rhabdoid phenotype in adult renal cell carcinoma and to determine its origin by genetic analysis. DESIGN: We performed histologic, immunophenotypic, and genetic analyses on 5 cases of adult renal cell carcinoma with rhabdoid differentiation, 3 samples of adjacent conventional (clear cell) tumor, and 6 conventional (clear cell) control tumors. RESULTS: Rhabdoid tumors differed from conventional (clear cell) carcinoma as follows: (1) macroscopically, rhabdoid tumors were solid white uniform masses; (2) microscopically, they had large rhabdoid cells with abundant eosinophilic cytoplasm, reduced lipid content, and the absence of a branching vascular pattern; and (3) biologically, they had a high metastatic potential. Despite these differences, loss of chromosome 3p in both the rhabdoid and clear cell carcinoma samples from 1 patient suggested a clonal origin. An identical mutation of the VHL gene in both rhabdoid and clear cell tumor samples from 2 patients confirmed a clonal origin for the histologically distinct tumor types in those cases. CONCLUSION: Adult rhabdoid renal cell carcinoma can in some cases arise from conventional (clear cell) renal carcinoma and should be considered a clinically important form of renal cell carcinoma separate from, but analogous to, sarcomatoid change.

Adenocarcinoma, Clear Cell↗

PubMed1999

An orthotopic in vivo model of human pancreatic cancer.

BACKGROUND: Pancreatic cancer is a highly lethal disease that frequently presents in advanced stages. For most patients, treatment with great clinical efficacy does not exist. Relevant in vivo models to test novel therapies are highly desirable. METHODS: The human pancreatic ductal adenocarcinoma cell line Panc-1 was injected intraperitoneally into SCID mice. The pattern of the resulting peripancreatic as well as metastatic disease was examined. Survival experiments after chemotherapy with gemcitabine or doxorubicin, and after immunotherapy with p53-specific cytotoxic T lymphocytes were performed. RESULTS: All animals developed isolated pancreatic tumor implants within 48 hours after injection. After the formation of invasive pancreatic tumor nodules, peripancreatic and portal adenopathy developed, causing biliary obstruction. All tumor-bearing animals died of disease within 5 to 12 weeks. Survival after gemcitabine treatment and after p53-CTL injection was significantly prolonged, with some animals remaining tumor-free. Doxorubicin treatment did not yield extended survival, but led to significant toxicity. CONCLUSION: Intraperitoneal injection of Panc-1 cells into SCID mice produces a quasi-orthotopic tumor development model that shares many characteristics with human pancreatic cancer. The ease of cell injection, avoidance of cumbersome surgical intervention with its resulting mortality, and the reliable development of obstructive jaundice as a dependent comorbid factor render this a useful model for in vivo testing of novel therapeutic approaches to pancreatic cancer. Our initial therapeutic studies demonstrate that in vitro antitumor efficacy against Panc-1 cancer cells does not necessarily predict the in vivo response, highlighting the preclinical experimental value of this model.

Adenocarcinoma↗