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PubMed1997

Rate of PSA rise predicts metastatic versus local recurrence after definitive radiotherapy.

OBJECTIVE: A rising prostate specific antigen (PSA) following treatment for adenocarcinoma of the prostate indicates eventual clinical failure, but the rate of rise can be quite different from patient to patient, as can the pattern of clinical failure. We sought to determine whether the rate of PSA rise could differentiate future local versus metastatic failure. METHODS AND MATERIALS: Two thousand six hundred sixty-seven PSA values from 400 patients treated with radiotherapy for localized adenocarcinoma of the prostate were analyzed with respect to PSA patterns and clinical outcome. Patients had received no hormonal therapy or prostate surgery and had > 4 PSA values post-treatment. PSA rate of rise, determined by the slope of the natural log, was classified as gradual [< 0.69 log(ng/ml)/year, or doubling time (DT) > 1 year], moderate [0.69-1.4 log(ng/ml)/year, or DT 6 months-1 year], or rapid [> 1.4 log(ng/ml)/year, or DT < 6 months]. RESULTS: Sixty-one percent of patients had non-rising PSA following treatment; 25% of patients with rising PSA developed clinical failure, and 93% of patients with clinical failure had rising PSA. The rate of rise discerned different clinical failure patterns. Local failure occurred in 23% of patients with moderate rate of rise versus 7% with gradual rise (p = 0.0001). Metastatic disease developed in 46% of those with rapid rise versus 8% with moderate rise (p < 0.0001). By multivariate analysis, in addition to rate of rise, PSA nadir and rate of decline predicted local failure; those with post-treatment nadir of 1-4 ng/ml were five times more likely to experience local failure than nadir < 1 ng/ml (p = 0.0002). Rapid rate of rise was the most significant independent predictor of metastatic failure. CONCLUSIONS: The rate of PSA rise following definitive radiotherapy can predict clinical failure patterns, with a rapidly rising PSA indicating metastatic recurrence and moderately rising PSA local recurrence. This information could potentially direct therapy; if the rise predicts metastatic failure hormonal therapy could be considered, while aggressive salvage therapy may benefit subclinical local recurrence identified by a moderate rate of PSA rise.

Adenocarcinoma↗

PubMed1992

Patterns of basement membrane laminin distribution in nonneoplastic and neoplastic thyroid tissue.

Laminin, a major basement membrane component, is typically absent or partially lost around the epithelial elements of most invasive carcinomas. To evaluate the distribution of laminin in both primary and metastatic thyroid tumors, we studied 14 benign thyroid lesions (eight adenomas, two Graves' disease, two Hashimoto's thyroiditis, one adenomatous hyperplasia, one nodular goiter), 20 carcinomas (seven papillary, six tall cell variant, four follicular, three Hürthle), and eight metastases (five tall cell variant, three follicular) utilizing a polyclonal antibody against highly purified, nidogen-free laminin. All benign lesions showed positive, linear immunostaining along basement membranes. Partial loss or absence of laminin was seen in the solid areas of all types of thyroid carcinomas examined; well-differentiated papillary and follicular tumors, as well as papillary and follicular areas of more poorly differentiated neoplasms, maintained linear laminin immunostaining in the papillary cores beneath the epithelial cells and around follicles. A similar correlation between laminin deposition and architectural organization was seen in metastatic lesions. Hürthle cell carcinomas had a unique fragmented, pericellular immunostaining pattern around individual tumor cells, suggesting uncontrolled laminin synthesis. Our findings suggest that preservation of laminin production in thyroid tumors reflects their degree of differentiation and that absence of laminin correlates with lack of structural organization rather than reflecting invasive and metastatic potential.

Basement Membrane↗

PubMed1988

[Pulmonary manifestations of alveolar soft part sarcoma; bronchial arterial embolization for hemoptysis].

Alveolar soft part sarcoma is a rare soft tissue tumor arising in extremities. The universal tendency for late widespread metastasis to lung, bone and brain, make the treatment of this tumor a particular challenge. This time, we performed the intra-arterial infusion of MMC and bronchial arterial embolization by spongel for hemoptysis of this metastatic lung tumor. Rosenbaum has reported the characteristics of angiogram of the metastatic brain tumor. In our case, bronchial arteriography showed the manifest hypervascular pattern "rosary form," "pooling" and "B-P shunt." These findings should yield benefits for the diagnosis and treatment of this metastatic lung tumor.

Adult↗

PubMed1983

Distribution of cardiac output during development of two metastasizing murine tumors.

The study of cardiac output (CO) distribution to tumors and metastases is of interest for a better understanding of tumor biology and for pharmacological approaches. A radioactive microsphere method was developed to asses CO distribution in C57BL/6J mice bearing syngeneic 3LL or BALB/c mice with JWS. At the initial stages of cancer growth, the CO relative fractions per g of tissue (%CO/g) to 3LL and JWS were similar to those in surrounding tissues. In both tumors a positive, significant correlation was found between tumor weight and tumor CO fraction, but %CO/g was lower in 3LL 2 and 3 weeks after transplantation, whereas it did not change in JWS. Indeed, much larger necrotic areas developed in 3LL than in JWS. The %CO/g to the lungs increased in both models when metastases were not yet visible; subsequently, the appearance of lung nodules was accompanied by a decrease of %CO/g in JWS and a further increase in 3LL. This corresponded to the much higher ratio of metastatic to intact lung tissue in JWS than in 3LL. In fact, isolated lung metastases had a significantly lower blood supply than the surrounding tissue. This might be due to a different vascularization pattern and/or smaller amounts of vasodilator substances being produced by metastatic nodules; the latter is suggested by lower generation of prostacyclin activity in isolated lung metastases than in intact pulmonary tissue.

Animals↗

PubMed1999

Metastases detected at the time of diagnosis of primary pediatric extremity osteosarcoma at diagnosis: imaging features.

BACKGROUND: The authors performed a retrospective study to estimate the incidence rate of metastatic disease at the time of diagnosis of extremity osteosarcoma (OS), to characterize its pattern of presentation, and to identify factors predictive of survival within a cohort of patients with pulmonary metastatic disease at diagnosis. METHODS: From the institutional solid tumor database, the authors identified all patients diagnosed with extremity OS since CT became available at the study institution (1977). The authors recorded patient demographics, the site of primary disease, the histologic subtype of OS, and the presence of metastases at diagnosis. In those patients with pulmonary metastases at diagnosis, the presence of calcifications, the primary tumor volume, the number of pulmonary lobes with disease, and the number of pulmonary nodules were recorded. RESULTS: Of an evaluable population of 215 patients, 32 (15%) had bone or pulmonary metastases at diagnosis, of whom original imaging from 28 patients was available for review. Osteoblastic histology correlated with lung metastases at diagnosis (P = 0.049). One of the 32 patients had a solitary bone metastasis without lung metastases. Four of 28 patients (14%) with original imaging available had calcifications within the pulmonary nodules. Both the number of nodules and the number of lobes involved were found to be significant predictors of survival (P = 0.0009 and P = 0. 04, respectively); multiple nodules were bilateral in 61% of patients. CONCLUSIONS: The rate of incidence of computed tomography detected pulmonary metastases was found to be 14% (31 of 215 patients) at diagnosis and 0.5% (1 of 215 patients) for bone metastases in patients with primary extremity OS. Pulmonary metastases usually are multiple and bilateral and infrequently calcify. The number of nodules and lobes involved are predictors of patient survival.

Adolescent↗

PubMed1995

Glycoconjugate profile and CD44 expression in human melanoma cell lines with different metastatic capacity.

Changes in glycoconjugate production have been reported for tumor cells. In this study, we investigated the glycoconjugate expression pattern in normal human melanocytes and in a panel of 6 human melanoma cell lines with different metastatic capacity after s.c. inoculation into nude mice. Glycoconjugates were labeled in vitro with [35S] sulphate and [3H] glucosamine, purified from cells and culture medium by column chromatography and identified by treatment with specific glycosidases. Characterization of the purified glycoconjugate fractions as well as alcian-blue staining of xenograft lesions revealed that hyaluronic acid (HA) is the main glycoconjugate produced by all cell lines. Highly metastatic cell lines expressed higher levels of HA than melanocytes and than weakly metastatic or non-metastatic cell lines. In addition, a shift in dominance from chondroitin-sulphate proteoglycan to heparan-sulphate proteoglycan was observed with increasing metastatic capacity. We also studied the expression and binding activity of the HA receptor CD44. Immunoprecipitation experiments indicated high CD44 synthesis only in highly metastatic cell lines, but FACS analysis demonstrated approximately the same surface expression in melanocytes as in all cell lines. Adhesion assays to immobilized HA showed that CD44 can be present in an inactive or an active conformation. Our data suggest that a combination of increased HA production and the expression of CD44 on the cell surface may be associated with high metastatic potential of human melanoma cell lines in nude mice.

Animals↗

PubMed1985

Biology of metastasizing ameloblastoma.

The present report of a malignant metastasizing ameloblastoma and a critical review of literature was undertaken in an attempt to better understand the biological potential and behavior of this rare tumor and thus to facilitate its clinical management. Most of the 26 patients with a proven malignant ameloblastoma including the present case had developed multiple recurrences. The lung was the most frequent metastatic site (88%) followed by regional lymph nodes (27%). Furthermore metastases were observed in some cases in the bone, brain, kidney, small intestine and liver. The interval between diagnosis of tumor and manifestation of metastases was long with a median of 11.1 years. The average survival time was 13.1 years. By contrast, the interval between diagnosis of metastatic disease and death was relatively short (median: 2.6 years). The histologic and cytologic pattern of malignant ameloblastoma and of its metastases was not significantly different from that of non-metastatic ameloblastoma. Because of the lack of morphological criteria of malignancy the biological behavior of ameloblastomas cannot be predicted. It is difficult to be certain which factors are important in the delayed induction of metastases. It is suspected that ameloblastomas possess an inherent low grade malignancy which is stimulated by multiple recurrences. It is further assumed that the metastatic tumor cells have a slow growth rate resulting in late clinical manifestation of metastases. When lung metastases occur we recommend their surgical removal in order to prolong live expectancy or even to obtain a curative effect.

Adult↗

PubMed1978

Effusive-constrictive hemodynamic pattern due to neoplastic involvement of the pericardium.

Eight patients with metastatic malignancy of the pericardium who demonstrated the hemodynamics of subacute effusive-constrictive pericarditis were studied. All patients had clinical evidence of cardiac tamponade due to malignant pericardial effusion and were referred for therapeutic pericardiocentesis. In six in whom pericardiocentesis was successfully performed, right atrial pressure remained elevated after pericardiocentesis and return of the intrapericardial pressure to zero; in these patients, hemodynamic data were initially compatible with tamponade but suggested constriction after removal of the pericardial fluid. In the remaining two patients, echocardiography revealed pericardial fluid, but attempted pericardiocentesis was unsuccessful. In these two patients, the hemodynamic data suggested pericardial constriction; subsequent pathologic examination revealed neoplastic involvement of the visceral pericardium. Thus, subacute effusive-constrictive pericarditis, previously recognized as a complication of tuberculosis or mediastinal radiation, may also be due to metastatic malignancy. The syndrome can readily be demonstrated when right heart catheterization is performed in conjunction with pericardiocentesis.

Cardiac Tamponade↗

PubMed1998

The normal structure and function of CD44 and its role in neoplasia.

CD44 is a transmembrane glycoprotein, the variant isoforms of which are coded for by alternative splicing, with the most prolific isoform being CD44 standard. CD44 is found in a wide variety of tissues including the central nervous system, lung, epidermis, liver, and pancreas, whereas variant isoforms of CD44 (CD44v) appear to have a much more restricted distribution. Variants of CD44 are expressed in tissues during development, including embryonic epithelia. Known functions of CD44 are cellular adhesion (aggregation and migration), hyaluronate degradation, lymphocyte activation, lymph node homing, myelopoiesis and lymphopoiesis, angiogenesis, and release of cytokines. The functions of CD44 are principally dependant on cellular adhesion in one setting or another. The role of CD44 in neoplasia is less well defined, although metastatic potential can be conferred on non-metastasising cell lines by transfection with a variant of CD44 and high levels of CD44 are associated with several types of malignant tumours. The physiological functions of CD44 indicate that the molecule could be involved in the metastatic spread of tumours. Many studies have investigated the pattern of CD44 distribution in tumours and some observations suggest that certain cells do not use CD44 in tumorigenesis or in the production of metastases. However, the data are extremely conflicting, and further studies are needed to establish the prognostic value of CD44 and its variant isoforms. The precise function of CD44 in the metastatic process and the degree of involvement in human malignancies has yet to be established fully.

Antigens, Neoplasm↗

PubMed1976

[Carcinoid tumor associated with osteoblastic metastasis and Cushing's syndrome].

This paper tries to group previous ideas related to: 1. The high possibility of metastatic disease to bone from carcinoid tumor to show a blastic pattern. 2. Cushing's syndrome can be secondary to non endocrine neoplasms. Both of these entities were present in the case being discussed which had a metastatic carcinoid but the primary site was not established.

Adult↗

PubMed1997

Cytodiagnosis of amelanotic metastatic malignant melanoma: an immunocytochemical study.

Malignant melanomas are known to present diverse patterns and this can result in considerable difficulties for an interpretation of malignancy type from cytohistologic material. Such difficulties are further compounded, if melanin pigment cannot be demonstrated by conventional histochemical stains; unfortunately many cases do exhibit this feature, especially in its metastases. This study was designed to review cases of amelanotic metastatic malignant melanomas in a variety of cytologic samples which were received from 40 patients with a known history of malignant melanoma. Cytomorphologically, the cases were classified as classical, carcinoma-like, spindle cell type, lymphoma-like, and undifferentiated type (Table I). While in 36 of the cases, the diagnosis of metastases from a melanoma was confirmed based on an immunopositivity to a variety of melanoma markers (Table III), in four of the cases, the immunostaining indicated metastases from another primary source, which was subsequently found. Based on our study, we are of the opinion that an immunologic characterization is useful to conclusively diagnose the majority of cases of metastatic amelanotic malignant melanomas. Furthermore, we feel that a reliance on a single melanoma marker is not justified, and a panel of antibodies should be used to distinguish a metastatic amelanotic malignant melanoma from other metastatic neoplasms.

Adolescent↗

PubMed2002

Differentially expressed genes identified in human melanoma cell lines with different metastatic behaviour using high density oligonucleotide arrays.

The increasing incidence of melanoma and the lack of effective treatment, with the exception of tumour excision before the onset of the metastatic phase, make it important to identify genes that may function as new molecular markers for diagnosis and/or prognosis or as new targets for therapy. Recently, a new technique using high density oligonucleotide arrays has been developed to simultaneously screen for the expression of thousands of genes. We used this technique to compare the mRNA expression patterns of two human melanoma cell lines with different metastatic behaviour. Eight differentially expressed genes, namely apolipoprotein CII, tyrosinase-related protein 1, transforming growth factor-beta superfamily, subtilisin-like protein, elongation factor 1 alpha2, alpha2-macroglobulin, human cell division cycle 10 and serine/threonine protein kinase (DYRK1A), were selected to validate the array results by Northern blotting and reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, a reliable correlation between differential expression of these genes in the melanoma cell lines and in fresh lesions of melanocytic tumour progression was demonstrated by RT-PCR analysis. Altogether, our data indicate that high density oligonucleotide arrays are a valuable and reliable tool to screen for differentially expressed genes, and that our study may be considered a basic step in the characterization of genes that are involved in the (malignant) progression of melanoma.

Blotting, Northern↗

PubMed1977

Uptake of bone imaging agents by diffuse pulmonary metastatic calcification.

Three cases of diffuse lung uptake of the bone scanning agent 99mTc diphosphonate, which appears to reflect metastatic pulmonary calcification, are described. Each patient had hypercalcemia and renal failure. Clinical features common to patients with this scan pattern were ascertained from a review of the literature. Renal failure was present in all, and the majority have had hypercalcemia. The bone scan may prove to be a valuable adjunct to the diagnosis of metastatic pulmonary calcification; this characteristic pattern should be more widely appreciated.

Adolescent↗

PubMed1999

Cytodiagnosis of hepatocellular carcinoma in fine-needle aspirates of the liver: its differentiation from reactive hepatocytes and metastatic adenocarcinoma.

Fine-needle aspiration (FNA) cytology is a useful tool for diagnosis of primary malignancies and metastatic lesions of the liver. However, well-differentiated hepatocellular carcinoma (HCC) may resemble benign/reactive hepatocytes, and less differentiated HCC may simulate poorly differentiated adenocarcinoma, leading to difficulties in interpretation of aspirates from liver. To determine the subtle cytomorphological features which can differentiate these lesions, ultrasound-guided FNA smears from 86 cases of liver malignancy were subjected to detailed cytologic assessment. These included 20 cases of HCC, 38 cases of metastatic adenocarcinoma, and 28 cases of benign/reactive hepatocytes. The important features for separating HCC or well-differentiated HCC from benign/reactive hepatocytes were excessive cellularity, trabecular pattern vs. thin cords of hepatocytes, nuclear pleomorphism, atypical stripped nuclei, and macronucleoli (P < 0.001 to < 0.0001). The most significant features for differentiating HCC from metastatic adenocarcinoma were trabecular growth pattern, hepatocytic cells vs. columnar/cuboidal cells, eosinophilic granular cytoplasm, lipid vacuoles, bile pigments, and atypical stripped nuclei (P < 0.001 to < 0.0001). The cytomorphological features which may distinguish poorly differentiated HCC from poorly differentiated adenocarcinoma were polygonal (hepatocytic) cells, eosinophilic granular cytoplasm and lipid vacuoles in HCC, and columnar/cuboidal cells and acinar/glandular formation in adenocarcinoma (P < 0.05 to < 0.001). Diagn. Cytopathol. 1999;21:370-377.

Adenocarcinoma↗

PubMed2000

Foamy gland pattern of pancreatic ductal adenocarcinoma: a deceptively benign-appearing variant.

Pathologic diagnosis of pancreatic adenocarcinoma is frequently a challenge, particularly in small biopsies, frozen sections, and in metastatic foci. Here we report a deceptively benign-appearing and morphologically distinctive pattern of ductal adenocarcinoma with prominent microvesicular cytoplasm, giving the cells a foamy appearance similar to that described in the prostate (Am J Surg Pathol 1996;20:419). This variant, which we refer to as foamy gland pattern (FGP), was frequently misdiagnosed in frozen sections or biopsies and its pathologic stage underestimated in surgical specimens. Histologically, the diagnostic features were: (1) white and crisply foamy, "microvesicular" cytoplasm; (2) often basally located and compressed, hyperchromatic nuclei reminiscent of endocervical glands (and so-called "adenoma malignum") or gastric foveolar glands; (3) irregular nuclear contours forming wrinkled (raisinoid) nuclei in some areas; and (4) a distinctive chromophilic condensation of the cytoplasmic material in the luminal aspect of the cells forming a brush border-like zone (BLZ). Histochemically, this BLZ was positive for mucicarmine, alcian blue, and high iron diamine, but not PAS. The remainder of the cytoplasm was negative for all these stains. In contrast, benign mucinous ducts, which constitute the major differential diagnosis, had more homogeneous acidophilic cytoplasm, lacked BLZ, and showed cytoplasmic staining with PAS. Immunohistochemically, the tumor cells were diffusely and strongly positive for CEA and cytokeratin 8 whereas B72.3 staining was focal and weak. MUC1 staining was largely confined to the BLZ. MUC2 was negative. P53 staining was detected in 16 of the 20 cases studied and was strong and diffuse in five. K-ras mutation was detected in 6 of 8 cases studied. The clinical findings in the 20 patients in this study (4 pure and 16 mixed with usual ductal carcinoma) did not appear to differ significantly from those of ordinary ductal adenocarcinoma of the pancreas. Eleven patients were men and nine were women; the mean age was 62 years and the mean tumor size was 4.4 cm. Follow-up information was available in 17 patients of whom 7 were alive at an average follow up of 23 months (range, 7-104 mos), and 10 were dead of disease at a median follow up of 15 months (range, 4-42 mos). The median survival of the four patients with pure FGP was 18 months. The median survival did not appear to be significantly longer than that of the patients with resectable ordinary ductal adenocarcinoma in the authors' experience (109 patients, median survival of 12 mos, p = 0.48). In conclusion, foamy gland pattern of invasive pancreatic ductal carcinoma is morphologically distinctive and is prone to misdiagnosis as a benign process. The pathologic stage is often underestimated as a result of the lack of its recognition and misinterpretation as mucinous ducts. Careful attention to its microscopic features is adequate for accurate diagnosis. Histochemical and immunohistochemical stains are useful in confirming the diagnosis of malignancy in challenging cases.

Adult↗

PubMedDate not supplied

[Comparative study of histopathological patterns of primary tumour and pulmonary metastases of malignant tumours in children and adolescents after complex therapy].

The histopathological features of the primary site and 102 pulmonal metastases were compared in the material from 40 malignancies in children and adolescents. All patients were treated by chemotherapy. Among the malignancies 30 were osteogenic sarcomas. A great histological variability in the multiple metastases removed at one surgical procedure and also in the metastases removed in the subsequent surgeries, were found. Summing up, the whole investigation; in 61.8% of metastatic focusses no difference was found in the histopathological patterns seen at the primary site and pulmonary metastases, in 17.6% total regression was observed, in 13.8% dedifferentiation and in 6.8% maturation of the tumours tissue were observed.

Adolescent↗

PubMed1991

Patterns of presentation of breast disease over ten years in a specialised clinic.

A clinic specialising in breast disease has been surveyed over a decade. Detailed information has been collected on 3,500 women with benign breast disorders and 950 with breast cancer. Over this time, the demand for and utilisation of this facility has increased steadily. Over the ten years, there has been a trend for a higher proportion of breast cancers to be smaller in size and for fewer cancers to be locally advanced or metastatic at presentation. Critical appraisal of referral and consultation patterns indicates that the original aims of establishing this clinic have not been maintained. Paradoxically, this is a result of the success of the exercise. Measures which might lead to a higher proportion of patients with breast cancer being managed at the Breast Clinic rather than a General Surgical Outpatient Clinic are discussed.

Adult↗

PubMed1994

[High-resolution x-ray computed tomography of bronchiolo-alveolar carcinoma].

Bronchioloalveolar cell carcinoma may cause three main patterns on CT: solitary nodule, parenchymal consolidation, and multicentric disease. The nodules usually have spiculated margins and frequently contain bubble-like lucencies or pseudo-cavitation. When presenting as consolidation, this is due mainly to mucin secretion and results in areas of lower attenuation than soft tissue. Multicentric disease is characterized by the presence of multiple nodules which may mimic metastatic disease. Although bronchioloalveolar cell carcinoma may cause different patterns on high-resolution CT, certain CT findings are sufficiently characteristic to suggest the underlying diagnosis.

Adenocarcinoma, Bronchiolo-Alveolar↗