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Radiographic features of osseous metastases of soft-tissue sarcomas.

In contrast to most other neoplastic processes of bone, in our study osseous metastases from soft-tissue sarcomas (STS) were more reliably detected by radiography than by scintigraphy. The radiographic manifestations of 65 skeletal metastases in 23 patients with STS were reviewed. Although most metastases (88%) were osteolytic, eight (12%) lesions were osteoblastic. The destructive patterns were geographic in 29%, moth-eaten in 55%, and permeative in 12% of the lesions. The axial skeleton was most commonly involved. In the long bones the diaphyses were the predominant sites of involvement. The bony cortex was frequently breached, with resultant soft-tissue swelling and pathologic fractures. Noteworthy features included subarticular location, involvement of the sacroiliac joint, and an expansile appearance.

Adolescent↗

Optic nerve/sheath enlargement. A differential approach based on high-resolution CT morphology.

A wide variety of neoplastic and non-neoplastic processes can cause the intraorbital optic nerve and sheath to be enlarged on CT. The authors reviewed a large number of high-resolution CT scans and divided enlargement into three groups: tubular, fusiform, and excrescent. Further subdivision was possible by determining whether distinct optic nerve lucency was present or absent.

Cranial Nerve Neoplasms↗

Pediatric musculoskeletal MR imaging.

In a review of the indications and uses for magnetic resonance (MR) imaging of the pediatric musculoskeletal system, MR evaluation of conditions unique to the pediatric musculoskeletal system were emphasized. Indications for MR imaging of the pediatric musculoskeletal system include evaluation of bone marrow, neoplastic processes, and periarticular disorders.

Bone Diseases↗

Second malignancies in pediatric patients: imaging findings and differential diagnosis.

Therapeutic advances in the treatment of pediatric neoplasms have improved the prognosis but have also increased the risk of developing rare second malignant neoplasms (SMNs). Primary neoplasms that are often associated with SMNs include lymphoma, retinoblastoma, medulloblastoma, neuroblastoma, and leukemia. The most common SMNs are central nervous system (CNS) tumors, sarcomas, thyroid and parotid gland carcinomas, and leukemia, particularly acute myeloblastic leukemia. Genetic predisposition, chemotherapy, and especially radiation therapy are implicated as pathogenic factors in SMN. All survivors of childhood cancer should have lifelong follow-up, preferably with magnetic resonance imaging, which does not require ionizing radiation and provides greater anatomic detail and resolution in the head and neck region and the CNS. A new or progressive lesion may represent recurrence of the primitive neoplastic process, late radiation injury, or, more infrequently, an SMN. Differential diagnosis can be very difficult, and outcome is often fatal. Treatment protocols should be modified to reduce the risk for SMN without compromising the effectiveness of initial therapy. Clinicians should individualize treatment for patients who are genetically predisposed to SMN. In addition, radiologists should be familiar with the long-term consequences of antineoplastic therapy to facilitate diagnosis and anticipate adverse outcomes.

Child↗

Cardiovascular complications of human immunodeficiency virus infection.

The heart and great vessels are not the sites most frequently affected by opportunistic infections and neoplastic processes in patients with acquired immune deficiency syndrome (AIDS). However, cardiovascular complications occur in a significant number of such patients and are the immediate cause of death in some. The spectrum of cardiovascular complications of AIDS that may be depicted at imaging includes dilated cardiomyopathy, pericardial effusion, human immunodeficiency virus-associated pulmonary hypertension, endocarditis, thrombosis, embolism, vasculitis, coronary artery disease, aneurysm, and cardiac involvement in AIDS-related tumors. To aid accurate diagnosis and appropriate treatment planning, radiologists should be familiar with the imaging appearance of each of these complications.

Adult↗

Verrucous carcinoma of the esophagus eluding multiple sets of endoscopic biopsies and endoscopic ultrasound: a case report and review of the literature.

A 56-year-old woman was noted to have a 5 cm to 6 cm long, irregular narrowing of the distal esophagus on an upper gastrointestinal series. Initial endoscopy revealed a polypoid mass in the distal esophagus and concurrent endoscopic ultrasound revealed changes typical of inflammation but no evidence of an obvious neoplastic process. Repeated biopsies revealed only inflammation with no evidence of malignancy. Only after prolonged acid suppression did biopsies reveal verrucous carcinoma of the esophagus. The patient underwent a trans-hiatal esophagectomy and has remained well with no evidence of progression since. Verrucous carcinoma is a rare variant of squamous cell carcinoma, taking on a papillary or warty appearance grossly. Histological diagnosis may be difficult because this tumour typically shows no high-grade dysplasia. Therefore, diagnosis can be challenging, often requiring multiple sets of endoscopic biopsies due to the overlying hyperkeratotic layer. Of the 20 cases that have been reported, this is the second to provide an endosonographic description and the first to describe a change in endoscopic appearance with acid suppression.

Biopsy↗

[Advances in radiography of the small intestine: computed tomography enteroclysis].

Computed tomography (CT) enteroclysis is a new technique consisting of helical CT of the abdomen and pelvis after administration of water through a nasojejunal tube and intravenous contrast, resulting in adequate distension and visualization of the small bowel wall. The use of this technique is especially recommended in patients with gastrointestinal bleeding of unknown etiology, possible neoplastic processes of the small bowel, partial small bowel obstruction, and inflammatory bowel disease. One-hundred consecutive patients underwent CT enteroclysis (multiple detectors; 8, 16, or 64) over a 1-year period for suspected lesions of the small bowel. Of these, 31 were positive: Crohn's disease (17), tumors (8), partial obstruction (2), radiation enteritis (1), sprue (1), pneumatosis cystoids (1), and dilatation of bowel loops (1). In 28 of the 31 patients, the findings were confirmed by pathology, endoscopy or clinical follow-up.

Adolescent↗

Matrix metalloproteinase activity modulates tumor size, cell motility, and cell invasiveness in murine aggressive fibromatosis.

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) regulate the degradation of extracellular matrix components and play important roles in the progression of select neoplastic processes. The locally invasive soft tissue tumor, aggressive fibromatosis (also called desmoid tumor), is caused by mutations resulting in beta-catenin-mediated T-cell factor (tcf)-dependent transcriptional activity. Because beta-catenin can regulate MMP expression, we investigated the expression of several MMPs and TIMPs in aggressive fibromatosis tumors that develop in Apc+/Apc1638N mice. Mmp-3 and Timp-1 were differentially regulated (5-fold and 0.5-fold, respectively) in tumors compared with normal fibrous tissue. Conditioned media from tumor cells showed an increased ability to degrade collagen, and inhibition of MMPs using GM6001 decreased the ability of the tumor cells to invade through Matrigel. Both the treatment of Apc/Apc1638N mice with GM6001 or crossing with a transgenic mouse that overexpresses Timp-1 resulted in a significant reduction in tumor volume. Surprisingly, overexpression of Timp-1 also resulted in a 50% increase in tumor number. Although TIMP-1 can induce growth stimulatory effects in some cell types, we found no difference in proliferation or apoptosis rate in cells from tumors that developed in the Timp-1-transgenic mice compared with mice that did not express the Timp-1 transgene, suggesting that TIMP-1 promotes aggressive fibromatosis tumor formation through an alternate mechanism. These data suggest that MMPs play a crucial role in regulating the invasiveness of mesenchymal cells and in modulating aggressive fibromatosis tumor progression. Because this is a locally invasive tumor, MMP inhibition could slow tumor growth and may prove to be an effective adjuvant therapy.

Animals↗

p38 regulates cyclooxygenase-2 in human mammary epithelial cells and is activated in premalignant tissue.

The immediate-early gene, cyclooxygenase-2 (COX-2), is induced in a variety of inflammatory and neoplastic processes and is believed to play an important role in tumorigenesis. In this study, we identify an important upstream regulatory pathway of COX-2 expression in variant human mammary epithelial cells (vHMEC), which has been shown to exhibit phenotypes important for malignancy. We find that the stress-activated kinase, p38, is phosphorylated and activated in vHMEC compared with HMEC and is responsible for the expression of COX-2 in vHMEC as cells grow in culture. Furthermore in this capacity, p38 acts to stabilize the COX-2 transcript rather than activate COX-2 transcription. Inhibition of p38 kinase, using a chemical inhibitor, down-regulates COX-2 and decreases cell survival. Examination of archived tissue from women with ductal carcinoma in situ reveals epithelial cells that not only overexpress COX-2 but also have an abundance of activated phospho-p38 in the nucleus and cytoplasm, mirroring the expression observed in vitro. These epithelial cells are found within premalignant lesions as well as in fields of morphologically normal tissue that surround the lesions. In contrast, low phospho-p38 staining was observed in the majority of normal tissue obtained from reduction mammoplasty. These data help define the regulation of COX-2 expression in early carcinogenesis and provide alternative candidates for targeted prevention of COX-2-induced phenotypes and breast cancer.

Apoptosis↗

Reassessment of id1 protein expression in human mammary, prostate, and bladder cancers using a monospecific rabbit monoclonal anti-id1 antibody.

Id proteins are a class of dominant-negative antagonists of helix-loop-helix transcription factors and have been shown to control differentiation of a variety of cell types in diverse organisms. Although the importance of Id1 in tumor endothelial cells is well established, the expression and role of the Id1 protein in human cancer cells is controversial. To explore this issue, we developed and characterized a highly specific rabbit monoclonal antibody against Id1 to assess its expression in human breast, prostate, and bladder malignancies. Our results show that in usual types of human mammary carcinomas, the Id1 protein is expressed exclusively in the endothelium. Interestingly, we detected nuclear expression of the Id1 protein in the tumor cells in 10 of 45 cases of poorly differentiated and highly aggressive carcinoma with metaplastic morphology. Similarly, only 1 of 30 prostate cancer samples showed Id1-positive tumor cells, whereas in almost all, endothelial cells showed high Id1 expression. Intriguingly, whereas normal prostate glands do not show any Id1 protein expression, basal layer cells of benign prostate glands in proximity to tumors expressed high levels of the Id1 protein. In contrast to the lack of Id1 expression in the usual types of mammary and prostate cancers, the majority of transitional cell bladder tumors showed Id1 protein expression in both tumor and endothelial cells. These results suggest that further refinement of Id1 expression patterns in a variety of tumor types will be necessary to identify and study the functional roles played by Id1 in human neoplastic processes.

Animals↗

Tissue distribution of human papillomavirus 16 DNA integration in patients with tonsillar carcinoma.

PURPOSE: Human papillomavirus 16 (HPV-16) has been implicated as a causative agent in a subset of head and neck squamous cell carcinomas (HNSCC). This study was undertaken to discern the distribution and timing of HPV viral integration during tumorigenesis of the upper respiratory tract. EXPERIMENTAL DESIGN: A tissue array was assembled from a consecutive group of 176 patients with HNSCCs. The array was evaluated by HPV-16 in situ hybridization and p16 immunohistochemistry. Patients with HPV-positive tonsillar cancers who had undergone bilateral tonsillectomies were selected for more complete mapping of viral integration. RESULTS: HPV-16 was detected in 38 of the 176 (22%) cases by in situ hybridization. When stratified by site of origin, HPV-16 was detected in 37 of 45 cancers arising from the oropharynx but in only 1 of 131 tumors arising from nonoropharyngeal sites (82% versus 0.8%, P < 0.00001). P16 expression was associated with the presence of HPV-16: 31 of 38 HPV-positive tumors exhibited p16 expression, whereas only 9 of the 138 HPV-negative tumors were p16-positive (82% versus 6%, P < 0.00001). In the bilateral tonsil sections, hybridization signals were strictly limited to the invasive cancers and associated dysplasias. P16 staining was widely distributed throughout the nonneoplastic crypt epithelium of individuals with and without tonsillar cancer. CONCLUSIONS: HPV-16 is strongly associated with carcinomas arising from the oropharynx, and integration is tightly coupled to the neoplastic process. Viral integration does not occur as a field alteration throughout normal tonsillar epithelium. P16 expression localizes to HPV-positive cancers, and is intrinsic to the specialized epithelium of the tonsillar crypts. For risk assessment, early cancer detection and disease surveillance, evidence of HPV-16 integration may represent a meaningful finding, whereas high p16 expression, by itself, may not.

Carcinoma, Squamous Cell↗

Bilateral nephroblastoma associated with a 3;17 translocation.

Cultured cells from the tumor of a child with bilateral nephroblastoma were studied cytogenetically. All mitoses observed showed the same male karyotype, 46,XY,t(3;17). This translocation constitutes a newly discovered rearrangement that has not been reported previously either in nephroblastoma or in other neoplastic processes.

Chromosome Banding↗

Expression of Lewis antigenic determinants in colorectal adenocarcinomas.

Expression of type 1 and type 2 chain Lewis antigens was studied in 32 rectal adenocarcinoma specimens; the results were correlated with the patients' Lewis phenotype and secretor status. In addition, the pattern of expression of these antigens was analyzed in adjacent and distant normal mucosa. We used an indirect immunofluorescence technique with p-phenylenediamine counterstaining (Oriol technique) and a panel of monoclonal antibodies directed against the different antigenic specificities. Normal distal colonic mucosa only expresses monofucosylated structures (Lea and X) arising from activity of the alpha 1-3,4-fucosyltransferase coded by the Le gene. Rectal adenocarcinomas also show Lea and X, but also reexpress blood group antigens ABH and exhibit difucosylated determinants (Leb and Y). The accumulation of mono- and difucosylated type 2 chain in neoplastic processes, independently of the Le and Se genes, could be due to the enzymes coded by reactivation of the H and X genes. Blood group antigens form a complex signal code, genetically regulated, which intervenes in differentiation, growth and cellular recognition processes, and which may undergo important modifications during malignant transformation. These alterations could be useful in the diagnosis and prognosis of some types of carcinoma.

Adenocarcinoma↗

Alpha-V/beta-3 and alpha-V/beta-5 integrin distribution in neoplastic kidney.

Integrins are transmembrane glycoproteins that mediate cell-cell and cell-matrix interactions. Altered integrin expression may contribute to tumor progression, invasiveness and metastases. The alpha-V/beta-3 (alpha v beta 3; osteopontin/ vitronectin receptor) has recently been implicated in neovascularization and tumor-induced angiogenesis. alpha v-Subunit also associates with beta 5 to form an alpha v beta 5-complex, another vitronectin receptor. We studied tissue distribution of alpha v beta 3-and alpha v beta 5-integrins, as well as alpha 1- and beta 1-subunits in nephrectomy samples from 7 subjects with localized renal cell carcinoma. Grossly and histologically uninvolved regions ('normal') from the same nephrectomy specimens were used for comparison. Integrin expression was studied with specific monoclonal antibodies and the immunoperoxidase technique. alpha v beta 3 was expressed in the glomerular epithelial cells, Bowman's capsule, vascular endothelium, and weakly in tubular epithelial cells. alpha v beta 5 had a similar distribution except for minimal expression on vascular endothelium. alpha 1-Expression was observed in mesangium and but weakly in Bowman's capsule. beta 1-Expression was seen in glomerular epithelial cells, Bowman's capsule, vascular epithelium and tubular epithelial cells. Unlike in 'normals', neoplastic expression was more heterogeneous alpha v beta 3 was expressed in tumor cells in 4/7 cases, vascular endothelium in 6/6, and in stroma in 4/7. alpha v beta 5 was weakly expressed in tumor cells in 4/5, vascular endothelium in 5/5, and stroma in 4/5 cases. alpha 1-Expression was seen in tumor cells in 3/7, vascular endothelium in 4/7 and in stroma in 7/7 cases. beta 1-Expression was seen in tumor cells in 7/7 cases, vascular endothelium in 7/7, and in stroma in 4/7 cases. This study delineates the pattern of expression of the alpha v beta 3-and alpha v beta 5-integrins in 'normal' and neoplastic human kidney. Variations in alpha v beta 3-and alpha v beta 5-integrin expression may play a role in normal and neoplastic processes of the kidney.

Adult↗

Acute phase response in bronchiectasis and bronchus carcinoma.

Measurement of the acute phase response in patients suffering from bronchiectasis, emphysema, bronchus carcinoma and various benign space occupying lesions was undertaken, using sensitive immunoradiometric assays for C-reactive protein and serum amyloid-A protein. In some patients with bronchiectasis, clinically judged to be in remission, the results show a major ongoing acute phase response. Such a response could predispose these patients to the development of reactive secondary amyloidosis. In bronchus carcinoma, the application of these measurements to judge the extent of tumour growth is limited as infection complicating obstruction is a more potent initiator of the acute phase response than the neoplastic process per se.

Adenocarcinoma↗

Acute phase response in bronchiectasis and bronchus carcinoma.

Measurement of the acute phase response in patients suffering from bronchiectasis, emphysema, bronchus carcinoma and various benign space-occupying lesions was undertaken, using sensitive immunoradiometric assays for C-reactive protein (CRP) and serum amyloid-A protein (SAA). In some patients with bronchiectasis, clinically judged to be in remission, the results show a major ongoing acute phase response. Such a response could predispose these patients to the development of reactive secondary amyloidosis. In bronchus carcinoma the application of these measurements to judge the extent of tumor growth is limited as infection-complicating obstruction is a more potent initiator of the acute phase response than the neoplastic process per se.

Amyloid↗

Evidence for the neoplastic involvement of monocytic, eosinophilic and basophilic lineages in acute myelomonocytic leukemia with eosinophilia.

To investigate the origin of cells observed in acute myelomonocytic leukemia with eosinophilia (M4E0), we carried out morphological and cytogenetic studies of colonies derived from leukemic precursors. Marrow cells from a patient with M4E0 at second relapse revealed an abnormal karyotype; 47,XY, +8, inv(16)(p13q22), 17p-. Cytogenetic studies of leukemic colonies showed the same karyotypic abnormality. The primary and secondary colonies consisted of monocytes, eosinophils and basophils. These results indicated that the neoplastic process in this patient originated in a stem cell capable of differentiation into at least monocytes, eosinophils and basophils.

Adult↗

Selenomethionine in the inhibition of a transplantable murine lymphoma: reflection on hepatic drug metabolizing enzymes.

This study attempts to determine whether selenomethionine treatment can improve the survival time of mice inoculated with Dalton's lymphoma (DL) and thereby to identify phase/phases of the neoplastic processes at which selenium exerts its maximal action as an anticancer agent. Accordingly, a maximum of 30.76 and 143% increase in survival was brought about by treatment of selenomethionine prior to lymphoma transplantation, in comparison to mice receiving selenomethione supplementation concurrently with inoculation of DL, and those tumor-bearing mice receiving no supplementation, respectively. Beneficiality of selenomethionine has also been studied by monitoring the continuous changes brought about by this compound on hepatic total cytochrome P-450 and b5 content, NADPH cytochrome c reductase, UDP glucuronyl transferase and glutathione S-transferase (GST) activities. These are important biotransformation enzymes and are altered significantly in neoplasia. The drastic increase in all the markers studied, excepting GST, was effectively counteracted by selenomethionine treatment (more before than concurrently), which sufficiently delayed and controlled the increase in those xenobiotic indices. The 112 and 78.78% induction in GST activity brought about by prior and concurrent treatment of selenomethionine, respectively, confirms the fact that inducers of GSTs are often antitumorigenic.

Animals↗