Neoplastic Features Research Articles

Cystic tumours of the pancreas.

Cystic pancreatic tumours may be misdiagnosed as pseudocysts. From August 1990 to January 1998, 21 patients (16 women) with a median age of 60 years underwent operation for a cystic mass in the pancreas with histological confirmation of neoplasia (six serous cystadenoma (SCA), three mucinous cystic adenoma (MCA), ten mucinous cystadenocarcinoma (MCAC), one ductal adenocarcinoma with cystic degeneration, one cystic islet cell tumour). While the lesion had been labelled as a pseudocyst in eight patients, only one patient (MCA in the pancreatic head) had had acute pancreatitis previously. In seven patients the computed tomogram (CT) lacked suspicious neoplastic features, while endoscopic retrograde cholangiopancreatography, angiography and percutaneous cyst fluid analysis were unhelpful or misleading in 16 of 18 investigations with respect to differentiating tumour from pseudocyst. Attempted operation for cure was performed in 18 patients despite diagnostic delays of up to 6 years and initial treatment with cystenterostomy in two cases. Retrospective review revealed that all 21 cystic neoplasms could be diagnosed before operation by a history excluding previous pancreatitis (20 of 21 patients) or a CT suspicious for neoplasia (14 of 21). The diagnosis relies more on absence of previous pancreatitis and a suspicious clinician who errs on the side of resecting a pseudocyst rather than watching or draining a cystic neoplasm.

Elongated non-neoplastic duodenal polyp: Endoscopic features

According to a well-established and widely accepted classification of intestinal tumors, protruding lesions of the duodenum are divided histopathologically into two categories: neoplastic and non-neoplastic.1 The latter category includes inflammatory, hamartomatous, and hyperplastic polyps. In the duodenum, however, there are polypoid lesions that cannot be specifically classified as any of these non-neoplastic types. These indeterminate lesions have been referred to as “unclassified polyps.” Three patients with duodenal polyps that were of the unclassified type were encountered. The polyps had markedly similar and uniform morphologic and histopathologic features.

Angioganglioglioma: A Transitional Form Between Angioglioma and Gangioglioma?

The authors describe for the first time an unusual cerebral tumor with unique clinical history, composed of 3 components: pilocytic astrocytoma, vascular proliferations similar to those described as arteriovanous malformations, and a neoplastic ganglion component. These three components were intimately entangled and created the tumor mass. Thus the authors propose the term angioganglioglioma for this entity. The relation to the historically defined anglioglioma and tumors related to ganglioglioma and dysembryoplastic neuroepithelial tumor is discussed. The authors believe that this lesion, in regard to the clinical presentation (long course of the disease, clinical symptoms), is closely associated with ganglioglioma and, with other morphological features, also to angioglioma. Further, it may constitute a new distinct clinicopathological entity with neoplastic and hamartomatous features.

New prognostic factors and developing therapy of cutaneous melanoma

The multiple molecular alterations underlying the neoplastic process and clinical characteristics of cutaneous melanoma are currently under intensive investigation. Recent studies have demonstrated that the levels of melanoma-associated proteins in tumor tissue or in patient serum can serve as new markers to predict disease outcome. Similarly, the expression of thousands of genes in melanoma tumors can be surveyed simultaneously using DNA arrays, allowing molecular profiling of individual tumors, which gives the possibility of classifying melanomas based on their biological diversity. Large clinical studies have also identified multiple prognostic factors, such as tumor ulceration, and led to development of a new, more precise melanoma staging system, which emphasizes the biological characteristics of the primary disease. These new findings may have an important role in earlier measurement of the clinical response and provide a basis for tailored melanoma therapy, the development of which will also be discussed in this review.

Cystic degeneration/Spongiosis hepatis in rats.

Cystic degeneration/spongiosis hepatis in rats has been proposed to be a preneoplastic and/or neoplastic lesion by some authors, because of its proliferative properties and persistent increased cell turnover rate in stop experiments using hepatocarcinogens, and the assumption that it can develop into a sarcoma. The neoplastic potential of cystic degeneration is questioned in this review article. Cystic degeneration, which appears to derive from altered Ito cells, does not have neoplastic histomorphologic characteristics, although it may be composed of cells with an increased mitotic index. In this regard, persistent proliferation is also seen with other nonneoplastic lesions. Arguments are presented to show that the induced, probably extremely rare sarcoma that was associated with cystic degeneration most likely derives from the very rare induced spherical Ito-cell aggregate with an unusually high cellular turnover rate in rats treated with hepatocarcinogens, and not from cystic degeneration. Also, in none of 12 referenced standard oncogenicity studies with chemically induced cystic degeneration was the lesion associated with mesenchymal (Ito-cell) tumors. Consequently, evidence is lacking that cystic degeneration in rats should be classified as a preneoplastic or neoplastic lesion. The 12 oncogenicity studies in rats with induced cystic degeneration showed a marked sex predilection, with males more likely to develop either spontaneous or chemically induced lesions. In these 12 studies, cystic degeneration was more often associated with hepatocellular hypertrophy or hepatotoxicity. rather than hepatocarcinogenicity. Thus, it is concluded that hepatocarcinogens induce cystic degeneration, not because they are carcinogenic. but because they have other effects on the liver, and that cystic degeneration may be a secondary/reparative change. Cystic degeneration in fish parallels the situation in rats in many respects, yet the existence of the lesion in other species, including man, is not as well supported. Based on the data presented in this review, spontaneous and induced cystic degeneration in rats and fish is not a preneoplastic or neoplastic lesion and risk assessment for man can be based on no-effect levels and safety margins, as for other nonneoplastic adverse effects that have no counterpart in man.

PLEUROPULMONARY BLASTOMA: An Aggressive Intrathoracic Neoplasm of Childhood

A case of a 4-year-old girl with pleuropulmonary blastoma is reported. Surgical resection of the tumor was performed and histologic examination revealed pleuropulmonary blastoma with rhabdomyosarcomatous differentiation. Postoperative chemotherapy was administered and 3 weeks after initiation of treatment protocol a second site of lesion in the retroperitoneum was revealed with extension to the mediastinum, which shared similar mesenchymal neoplastic characteristics to the previously diagnosed primary lesion. The girl died 4 1/2 months after initial evidence of disease because of brain metastasis, indicating a very aggressive neoplasm unresponsive to treatment.

Mixed Medullary-Follicular Thyroid Carcinoma: Molecular Evidence for a Dual Origin of Tumor Components

Mixed medullary-follicular carcinomas (MMFCs) are tumors of the thyroid that display morphological and immunohistochemical features of both medullary and follicular neoplasms. The histogenetic origin and possible molecular mechanisms leading to MMFCs are still unclear. To address these questions, we have isolated the two histological components of 12 MMFCs by (laser-based) microdissection, analyzed them for mutations in the RET proto-oncogene and allelic losses of nine loci on six chromosomes, and studied the clonal composition of MMFCs in female patients. Our results provide strong evidence that the follicular and medullary components in MMFCs are not derived from a single progenitor cell, because the seven tumors amenable for analysis consistently exhibited a different pattern of mutations, allelic losses, and clonal composition. We also demonstrate that follicular structures in MMFCs are often oligo/polyclonal and more frequently exhibit hyperplastic than neoplastic histological features, indicating that at least a subset of MMFCs are composed of a medullary thyroid carcinoma containing hyperplastic follicles.

Endometriomas: diagnostic performance of US.

To determine the diagnostic performance of specific ultrasonographic (US) features in discriminating endometriomas from other adnexal masses. Two sonologists independently reviewed the sonograms of 252 adnexal masses in 226 women and recorded US features by using a standardized checklist. The diagnostic performance of specific US features and overall reviewer impression in discriminating endometriomas from other adnexal masses were evaluated. There were 40 endometriomas. Diffuse low-level internal echoes were present in 38 (95%) endometriomas and 40 (19%) nonendometriomas (positive likelihood ratio, 5). The positive likelihood ratio for the diagnosis of endometrioma increased to 8 if masses with neoplastic features at gray-scale US were excluded, allowing identification of 30 endometriomas (75%). The presence of multilocularity or hyperechoic wall foci further increased the positive likelihood ratio to 48, allowing the identification of 18 endometriomas (45%). An adnexal mass with diffuse low-level internal echoes and absence of particular neoplastic features is highly likely to be an endometrioma if multilocularity or hyperechoic wall foci are present. A patient with a mass with diffuse low-level internal echoes and other US features may benefit from additional imaging.

Testicular encasement by retroperitoneal fibrosis: a rare testicular mass

A53-year-old black man presented with elevated serum creatinine and blood urea nitrogen levels, bilateral hydronephrosis, and an unremarkable physical examination (abdomen, flank, genitalia, rectum). Computed tomography (CT) of the abdomen/pelvis demonstrated a diffuse homogeneous mass encasing both ureters suggestive of retroperitoneal fibrosis (RF). The diagnosis was confirmed by biopsy (Fig. 1). He underwent bilateral percutaneous nephrostomy drainage and steroid administration. Bilateral ureterolysis with omental wraps was performed for persistent ureteral obstruction. Four years later, he returned with a painless left scrotal mass. Sonography demonstrated a solid homogeneous mass replacing the testicle. Serum tumor markers (HCG, AFP, LDH) were not elevated. A left radical orchiectomy was performed for a presumptive diagnosis of testicular malignancy (Fig. 2A). Pathologic examination revealed complete encasement of an atrophic testicle by a dense fibrous sheet involving the tunica vaginalis, which was histologically consistent with RF (Fig. 2B). There were no neoplastic features. CT of the abdomen/pelvis demonstrated residual RF without hydronephrosis.

Spinal hamartomas: a distinct clinical entity.

Congenital spinal hamartomas are defined as tumors of well-differentiated mature elements situated in an abnormal location. In this report, the authors document the clinical and pathological features of spinal hamartomas in 10 patients. Ten patients presented with midline dorsal malformations at birth, initially diagnosed as teratomas or myelomeningoceles. The locations of the masses were variable: two were located in the thoracic region, four at the thoracolumbar junction, two in the lumbar region, one at the lumbosacral junction, and one in the sacral region. The results of the neurological examination were normal in nine patients. All but one mass had intact skin and seven had palpable bone components. Neuroimaging studies revealed widening of the spinal canal, heterotopic bone located dorsally in some patients, and varying degrees of involvement of the intraspinal contents. During surgery, six patients were found to have involvement of the spinal cord or cauda equina. The pathological characteristics of the masses included three or more of the following: bone, cartilage, synovial membrane, urinary tract tissue, cyst wall, yellow or brown fat, and nerves. The well-differentiated cellular elements, which formed mature structures, along with the absence of primitive cellular components and neoplastic characteristics are more consistent with a diagnosis of hamartoma than teratoma. In this series, the authors describe a lesion that is overt on physical examination, yet can have occult spinal canal involvement. Complete neurosurgical evaluation is essential to provide appropriate treatment and prognosis.

Genetics Is Coming to Oncology

Picture the mechanisms that govern the behavior of a cell as an enormous puzzle. Each piece represents a critical function responsible for some aspect(s) of cellular behavior. In normal cells, all of the pieces fit perfectly. Those that touch one another represent communicating functions that carry vital chemical signals from one point to another in the cell. This function-to-function communication or signaling contributes to the normal control of growth and differentiation and the failure of a cell to develop neoplastic characteristics. In a cancer cell, some of the pieces do not fit, because of distortions of shape, size, or both. Others are lost altogether. Yet others are abnormally replicated, sometimes many times over. By comparison with that of a normal cell, the picture that emerges from a cancer cell puzzle is disorderly. However, it is still a picture of limited size and shape, and discoveries of the last 20 years

Microsatellite alterations in plasma DNA of small cell lung cancer patients.

Microsatellite instability is an important characteristic of many tumor types especially those associated with hereditary non-polyposis colorectal carcinoma (HNPCC) syndrome. Microsatellite alterations in 50% of primary small cell lung carcinoma (SCLC) have been found. These alterations were also found in the sputum. Because neoplastic characteristics such as decreased strand stability9 and ras mutations have been found in the plasma DNA of cancer patients, we looked for microsatellite alterations in the plasma of SCLC patients. A microsatellite alteration was present in 16 out of 21 (76%) SCLC tumors and in 15 out of 21 (71%) plasma samples. In one case, the alteration was present only in the plasma DNA. If confirmed in larger studies, microsatellite analysis of plasma DNA might constitute a new tool for tumor staging, management and, possibly, detection.

Preferential Hematopoiesis by Paroxysmal Nocturnal Hemoglobinuria Clone Engrafted in SCID Mice

In paroxysmal nocturnal hemoglobinuria (PNH), little is known about the molecular events leading to the clinical manifestations except for the hemolysis. To unfold the complex pathophysiology, it is necessary to elucidate the nature of the PNH clone. PNH exhibits an acquired stem cell disorder, a clonal expansion of affected cells, concomitant depression of normal hematopoiesis in bone marrow (BM), and, although infrequently, the development of leukemia. The PNH clone is thus expected to exhibit some neoplastic features. We report here that CD34+ hematopoietic progenitor cells of PNH-BM yielded blood cells of three lineages with PNH phenotype alone when transplanted into sublethally irradiated severe combined immunedeficient mice. The hematopoiesis persisted for more than 10 months and did not always need human cytokines. In contrast, the hematopoiesis by control grafts obtained from healthy volunteers required an intense cytokine treatment. This in vivo model defines the preferential hematopoiesis of pluripotent PNH progenitor cells, indicating the intrinsic growth abnormality of PNH clone.

Improved Tissue Culture Method for the Study of Prostatic Carcinoma: A Significant Diagnostic Tool

A new in vitro method for early detection of prostatic cancer is described. The results of tissue culture of prostatic epithelial cells harvested during digital rectal examination were compared with patient-matched biopsy findings in a double-blind study. An arbitrary combination of five culture parameters (displayed in vitro by cultured prostatic cells and related to neoplastic and differentiation features of the sample [growth capacity, proportion of epithelium and morphologic atypia of overlapping cells, multinucleated cells and vacuolized cells]), was created after two weeks of culture; this combination, referred to as the Global Tissue Culture Score (GTCS), ranged from 0 (negative result or benign behavior) to 15 (highly abnormal neoplastic behavior). The GTCS was significantly higher in biopsy-proven prostatic carcinoma than in other prostatic diseases. The combination of GTCS and patient age was highly sensitive and specific for a diagnosis of prostatic carcinoma, according to the biopsy results. Our findings indicate that the early diagnosis of prostatic carcinoma can be obtained by a tissue culture method which allows in vitro growth of epithelial cells harvested through digital rectal prostatic massage. This method is easy to perform, is non-invasive, is able to discriminate between biologically aggressive and non-aggressive neoplasms, and may be useful for mass screening of prostatic carcinoma in conjunction with digital rectal exam. Early diagnosis of prostatic carcinoma may maximize the potential curative value of radical prostatectomy or other forms of therapy for this highly prevalent cancer.

Adenylate Kinase in Tobacco Cell Cultures. II. Variability and Regulation of Isoform Activity Patterns in Different Cell Lines

Summary Specific activity and isoform patterns of adenylate kinase (AK) were investigated in tissue cultures of cloned tobacco cell lines that differed mainly in hormone requirement, proximate cause of hormoneautotrophy and neoplastic growth characteristics. Variations in the AK isoform pattern were related to growth and ageing processes, differentiation state of tissues, differences between culture cycles as well as the neoplastic characteristics of the cell lines. High specific AK activity and isoform patterns with dominating chloroplastic activities appeared as typical of green, photosynthetic and actively growing tissues (calli in growth phase, callus outer tissues). Lower specific AK activity and isoform patterns with dominating cytosolic activity were typical for senescent or non-photosynthetic tissue (calli in stationary phase, callus core tissues), but sometimes also occurred in entire young calli, apparently as a consequence of stress. This isoform pattern is therefore proposed as a stress marker in plant cell cultures. The isoform patterns of the different cell lines were analyzed in detail for the variations during different culture cycles and the differences appearing under optimal growth conditions. The observed characteristics were related to proximate cause of hormone-autotrophy and neoplastic state. The main differences appeared between normal and neoplastic, transformed tissues. Changes in compartmentation of AK activities under different metabolic situations are discussed with respect to the physiological characteristics of the cell lines, energy metabolism and ATP/ADP ratios of cellular compartments and the presumed role of AK in ageing and stress.

Tissue infiltration in a CD8 lymphocytosis syndrome associated with human immunodeficiency virus-1 infection has the phenotypic appearance of an antigenically driven response.

HIV-1 infection may initiate to an HLA-associated response designated diffuse infiltrative lymphocytosis syndrome, characterized by increased numbers of circulating CD8 T cells that infiltrate salivary glands, lungs, gastrointestinal tract, and kidneys. Since this response could either be an antigenically driven process induced by HIV-1 or a lymphoproliferation of cells with neoplastic or unusual features, we sought to define the phenotype of the cellular populations, the nature of tissue derangement, and the tissue localization of virus in diffuse infiltrative lymphocytosis syndrome. Circulating CD8 T cells were greatly increased while CD4 T cell numbers remained in the range found in asymptomatic seropositive persons. The majority of CD8 and CD4 T cells in both blood and tissues had the memory phenotype of CD29+ (beta 1 integrin) and CD11a+/CD18 (beta 2 integrin) expression, but lacked markers of recent activation. A proportion of the circulating CD8 T cells also expressed CD57 (Leu 7) but not other markers of natural killer cells. HIV-encoded proteins were identified in tissue macrophages located in periacinar areas of the salivary glands. CD54 (intercellular adhesion molecule-1), a ligand for the CD11a integrin, was strongly expressed on postcapillary venule endothelium within lymphoid foci, and HLA-DR molecules were found on limited regions of ductular epithelium adjacent to lymphoid aggregates. These findings suggest that (a) the visceral lymphocytic infiltration in diffuse infiltrative lymphocytosis syndrome is an antigen-driven, and MHC-determined, host immune response to an element associated with HIV-1 infection, and (b) that the specific adhesive molecule interactions mediating the cellular influx, as well as the subsequent tissue damage, reflect altered patterns of gene expression in tissues undergoing an immune response.

Spontaneous membrane potential oscillations in Madin-Darby canine kidney cells transformed by alkaline stress.

High pH is known to be associated with normal cell growth and neoplastic transformation. We observed that Madin-Darby canine kidney (MDCK) cells grown under sustained alkaline stress (pH 7.7) develop "foci" composed of spindle-shaped cells lacking contact inhibition and exhibiting only poor adhesion to the culture support. Foci-developing (F) cells were cloned and grown in control medium (pH 7.4), where they maintained their neoplastic features indicating a stable pH-induced genetic transformation. After F cells had been fused to giant cells with polyethylene glycol, the cell membrane potential (Vm) was measured by means of microelectrodes. In contrast to non-transformed MDCK cells, Vm of F cells showed spontaneous biorhythmicity caused by periodic opening of Ca2(+)-activated K+ channels. Spiking activity was blunted by the Ca2+ channel blocker nifedipine, by the K+ channel blocker Ba2+, by the Na+/H+ exchange blocker amiloride and its analogue ethylisopropylamiloride, and by an extracellular pH of 7.6 and 6.8. We conclude that MDCK cells transformed by sustained alkaline stress have lost their stable plasma membrane potential but, instead, exhibit endogenous Ca2(+)- and pH-sensitive oscillations.

Propagation and properties of Kaposiʼs sarcoma-derived cell lines obtained from patients with AIDS: similarity of cultured cells to smooth muscle cells

Cells derived from Kaposi's sarcoma (KS) were propagated in vitro using conditions which resulted in elimination of contaminating fibroblasts and the emergence of homogeneous cell populations which morphologically resembled smooth muscle cells and had neoplastic characteristics. In long-term culture, they differentiated into large ribbon-like cells with longitudinal fibrillarity of their cytoplasm. These fibrils stained red by Masson trichrome staining, and were reactive with antibodies to desmin. Dense bodies typical of myoblasts were observed in some cells by electron microscopy. The cells did not form capillary structures like endothelial cells, they lacked Weible-Palade bodies, and did not express the blood-clotting Factor VIII-related antigen or receptors for the lectin Ulex europaeus agglutinin I. They did express four other antigens, however, in common with endothelial cells. The cells did not form tumors in athymic nude mice; however, they formed colonies in soft agar, manifested tumor-like growth on muscle organ cultures, and were invasive in an artificial basement membrane invasion assay. The results indicate that a component of KS is closely related to leiomyoblasts and and has neoplastic properties.

Immunoblastic Lymphadenopathy (IBL)-Like T-Cell Lymphoma in a Child

We report the case of a 14-year-old Japanese boy with peripheral T-cell malignant lymphoma, showing progression from immunoblastic lymphadenopathy (IBL) to overt malignant lymphoma. He suffered recurrent fever, generalized lymphadenopathy, hepatosplenomegaly and maculopapular exanthema. Leukocytosis with eosinophilia and polyclonal hypergammaglobulinemia were observed during the aggressive course of the disease. In the early phase, human immunoglobulin and steroids improved the symptoms but did not induce complete remission, and the patient died one year after the onset of the illness. Four biopsies of lymph nodes revealed progression from IBL to CD4 positive T-cell lymphoma through IBL-like T-cell lymphoma. Though IBL-like T-cell lymphoma is defined as IBL with neoplastic features and overt T-cell malignant lymphoma progressed from IBL-like T-cell lymphoma is excluded from the definition, it may be preferable that such malignant lymphoma as our case should also be included in IBL-like T-cell lymphoma.

Carcinoembryonic proteins produced by Wilms' tumor cells in vitro and in vivo

A Wilms' tumor cell line (HFWT) was established after tissue culture of the Wilms' tumor which had developed in the left kidney of a five-month-old boy. The HFWT line has the following cyto-biological characteristics: 1. The cells have a spindle, round or polygonal shape with neoplastic and pleomorphic features that grew in multilayers without contact inhibition. 2. The cells show a stable proliferation, giving 95 passages within 4 years. 3. The chromosomes show a wide aneuploidy distribution, and the modal number was found in diploid range. The stem cells have a normal karyotyping, 46, XY. 4. Heterotransplantation into nude mice can be easily made, and anaplastic Wilms' tumor resembling the original tumor forms. 5. The principal tumor markers produced by the cells in large amounts in the conditioned culture media were carbohydrate antigen 125 (CA 125) and tissue polypeptide antigen (TPA). 6. A good correlation was found between enlargement of the tumor formed by heterotransplantation into nude mice and the levels of CA 125 and TPA in the serum of the nude mouse. No report on the study of tumor markers widely used in clinical treatment of Wilms' tumor has been available to us, but CA 125 and TPA are considered to be useful in the diagnosis and treatment of Wilms' tumor.