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PubMed2003

Myoepithelial neoplasia of the submandibular gland: case report and therapeutic considerations.

Tumors of the submandibular gland typically arise from the seromucinous acini, which make up the majority of the gland. The most common benign tumor of this structure is the pleomorphic adenoma, whereas the most common malignancy of the submandibular gland is adenoid cystic carcinoma. We describe an unusual case of a neoplastic process of the myoepithelial cells of the submandibular gland in a middle-aged woman. This rare tumor is most commonly diagnosed in the parotid gland and in the minor salivary glands of the hard palate; a review of the literature uncovered only 5 previous reports of myoepithelioma of the submandibular gland. Distinguishing myoepithelioma from benign pleomorphic adenoma and malignant myoepithelial carcinomas can be challenging. Immunohistochemical staining can help to distinguish between the benign neoplasms, but histologic features remain the "gold standard" for diagnosing the malignant tumors. Increasing use of immunohistochemistry panels to assess parotid neoplasms also suggests that myoepithelioma may be underrecognized.

Adenoma, Pleomorphic↗

PubMed1976

Von Recklinghausen neurofibromatosis and acute leukemia.

The leukemias are neoplastic processes that have been associated with a variety of genetic disorders. A case of an adolescent with both acute myelomonocytic leukemia and von Recklinghausen disease is presented, and the literature reviewed to show that these two diseases are associated. Although the number of cases in the literature suggests that in children with von Recklinghausen disease there is a greater risk of leukemia developing, prospective studies are needed to prove this point.

Adolescent↗

PubMed1998

Neoplastic involvement of granulocytic lineage, not granulocytic-monocytic, monocytic, or erythrocytic lineage, in a patient with chronic neutrophilic leukemia.

Chronic neutrophilic leukemia (CNL) is a very rare myeloproliferative disorder. To determine the neoplastic origin of CNL, morphological and cytogenetical studies were made of colonies derived from hematopoietic progenitors of a patient with CNL. The patient's hematopoietic progenitors spontaneously formed colonies consisting of mature granulocytes, and cytogenetical study of the colonies indicated chromosome abnormalities identical to those in the patient's bone marrow cells. Analysis of colonies consisting of granulocytes and macrophages, macrophages, or erythrocytes disclosed a normal karyotype. These results demonstrated that the neoplastic process in this patient with CNL originated in hematopoietic progenitors capable of differentiating only into granulocytes, and not granulocytes and monocytes, monocytes, or erythrocytes.

Cell Lineage↗

PubMed1997

Colon polyps.

Colon polyps may be single or multiple, noninherited or inherited, histologically may vary from inflammatory, hamartomatous, neurogenic, or adenomatous, and may be benign or malignant. The various recognized syndromes are discussed including their clinical presentation, malignant potential, and associated tumors. Recognition of these clinical syndromes will allow the clinician to categorize the patient and the relative risk. The discussion goes into the genetic studies identifying the adenomatous polyposis coli gene on chromosome 5 q21 and the identification of mutations arising in the DNA repair genes (MSA2, MLH1, PMSI, and M52) in the HNPCC syndrome. This identified two divergent pathologies, both involving "multiple hits" with mucosal cells going from normal to adenoma-dysplasia-carcinoma. The understanding of the multiple hit concept with the adenoma-dysplasia-carcinoma progression will aid in the further understanding of the broad neoplastic process.

Adenoma↗

PubMed1998

Integrins, cadherins, and catenins: molecular cross-talk in cancer cells.

In the past decade, there have been major advances in the understanding of some of the mechanisms underlying tumour differentiation, invasion, and metastasis, in which cell-cell and cell-matrix adhesion molecules play a critical role. Cadherin/catenin complex and the integrins are the prime mediators of cell adhesion in normal and transformed cells, cadherin/catenin being largely responsible for intercellular adhesion and integrins for cell-extracellular matrix interactions. Intercellular and cell-matrix adhesion mediated by cadherin/catenin and integrins is likely to play a role in the control of both structural morphology and functional differentiation; hence, any loss of this control mechanism may well facilitate the neoplastic process. Indeed, in cancer cells, there is a co-ordinated down-regulation of both integrins and cadherins which correlates with tumour dedifferentiation. However, the expression and cellular localization of catenins do not always correlate with cadherin expression, since the catenins are rather promiscuous molecules which interact not only with E-cadherin, but also with growth regulatory and signalling molecules such as epidermal growth factor receptor and the adenomatous polyposis coli gene product.

Cadherins↗

PubMed1999

TP53 alterations in relation to the cell cycle-associated proteins p21, cyclin D1, CDK4, RB, MDM2, and EGFR in cancers of the uterine corpus.

In the present study, TP53 alterations have been analysed and compared with the expression of the proteins p21, cyclin D1, cdk4, RB, EGFR, and MDM2 in 53 cancers of the uterine corpus. TP53 gene mutations analysed by CDGE/DGGE and direct sequencing showed a TP53 gene mutation in 18 per cent of the cases. TP53 gene mutations were not significantly related to overexpression or down-regulation of any of the proteins. Immunohistochemically, there was an increased protein level of TP53 in 77 per cent, p21 in 36 per cent, cyclin D1 in 45 per cent, cdk4 in 77 per cent, EGFR in 8 per cent, and MDM2 in 32 per cent of the cases. Expression of RB protein was normal in all cancers. Significant association of protein expression was seen between TP53 and MDM2 (p=0.005) and p21 and MDM2 (p=0.001). Furthermore, there may be an association between TP53 and p21 (p=0. 038) and cyclin D1 and cdk4 (p=0.045). The results revealed increased levels of TP53 protein in all MDM2-positive cases that did not show TP53 mutations, indicating TP53 protein stabilization and inactivation by complex formation with MDM2. In summary, the high number of cases showing an increased level of TP53 and cdk4 proteins suggests that these proteins play an important role in the neoplastic process in cancers of the uterine corpus.

Carcinoma↗

PubMed1999

Characterization of the role of IL-6 in the progression of prostate cancer.

BACKGROUND: We recently identified IL-6, a pleiotropic cytokine implicated in the neoplastic process of a variety of neoplasms, as a mediator of prostate cancer morbidity. In the present study, we investigated the expression of members of the IL-6 supergene family and related cytokines and the potential role of IL-6 in prostate cancer growth regulation. METHODS: Five established human prostate cancer cell lines were screened by ELISA for production of granulocyte colony-stimulating factor (G-CSF), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostatin M (OSM), tumor necrosis factor (TNF), interleukin-1 (IL-1), and granulocyte macrophage colony-stimulating factor (GM-CSF). Expression of the ligand-binding component of the IL-6 receptor, IL-6Rp80, was evaluated by ELISA and RT-PCR. Sequential immunoprecipitation and immunoblotting were performed to assay for expression of the signal-transducing component of the IL-6 receptor, gp130. The effects of IL-6 on cell growth were assessed by MTT assays. RESULTS: The three hormone-refractory cell lines, DU-145, TSU, and PC-3, secreted distinct combinations of cytokines (DU-145: IL-6, GM-CSF; TSU: IL-6, LIF; PC-3: IL-6, G-CSF, LIF, IL-1, GM-CSF), each uniformly expressing IL-6. In contrast, neither of the two hormone-dependent cell lines, LNCaP-ATCC and LNCaP-GW, secreted significant quantities of any of the cytokines analyzed. None of the cell lines secreted detectable quantities of OSM, CNTF, or TNF. All cell lines, irrespective of hormone status, expressed both Il-6Rp80 and gp130. Addition of IL-6 in vitro inhibited growth of hormone-dependent cells, but had no effect on hormone-refractory lines. Anti-IL-6 neutralizing antibody inhibited growth of hormone-refractory cells. CONCLUSIONS: IL-6 appears to undergo a functional transition from paracrine growth inhibitor to autocrine growth stimulator during progression of prostate cancer to the hormone-refractory phenotype.

Cell Division↗

PubMed1999

K-ras mutation and loss of heterozygosity of the adenomatous polyposis coli gene in patients with colorectal adenomas with in situ carcinoma.

BACKGROUND: The majority of colorectal carcinomas, if not all, arise from a benign adenoma. The DNA of the carcinomatous cells frequently has mutations in several genes. However, it is not exactly clear when during the neoplastic process each mutation develops. An adenoma with an area of in situ carcinoma provides an opportunity to evaluate genetic changes within a single neoplasia whose separate areas are comprised of both the benign adenoma as well as the malignant carcinoma. METHODS: Thirty-seven neoplasms with areas of both benign adenoma and in situ carcinoma were studied. Both portions were evaluated for loss of heterozygosity (LOH) of the adenomatous polyposis coli (APC) gene and for mutations in codons 12/13 of the K-ras oncogene using the polymerase chain reaction technique. RESULTS: Twenty-eight neoplasms showed no LOH in either portion whereas both portions of 4 neoplasms revealed a loss of heterozygosity. In three lesions the APC gene was normal in the adenomatous portion but LOH was present in the carcinomatous portion. Two neoplasms were uninformative for LOH of the APC gene. Thirteen neoplasms showed the wild-type pattern for the K-ras oncogene whereas 15 contained the identical mutation in both portions. Of the remaining nine neoplasms, six had a K-ras mutation in the adenomatous portion only and three had one pattern in the adenomatous portion and a different pattern in the in situ carcinoma portion. CONCLUSIONS: LOH of the APC gene is an early and persistent feature in the evolution of a benign colorectal adenoma into an in situ carcinoma. There is less consistency regarding K-ras mutations; one in five in situ carcinomas contains a K-ras mutation different from that observed in the adenomatous portion.

Adenomatous Polyposis Coli↗

PubMed1996

p53 expression and proliferative activity predict survival in non-invasive thymomas.

We performed p53 immunohistochemistry, DNA flow cytometry and analysis of the argyrophilic nucleolar organizer regions (AgNORs) in formalin-fixed, paraffin-embedded sections from 46 non-invasive thymomas and correlated the results with the traditional clinicopathologic features of the tumor. p53 immunopositivity was detected in 21 of 46 cases; it was not associated with any clinicopathologic features nor DNA content but significantly correlated with AgNOR counts. On univariate analysis, 10-year survival rates were 100% for p53-negative cases but only 71% for p53-positive cases and 93% for patients with low AgNOR counts but only 77% for patients with high AgNOR counts. Age, sex, histologic type, myasthenia gravis and DNA content did not correlate with survival. Our results indicate that p53 staining and evaluation of proliferative activity allow assessment of prognosis in non-invasive thymomas, when all of the other parameters are insufficient. Furthermore, the high rate of p53 expression in non-invasive thymomas suggests that abnormal p53 immunoreactivity may occur early in the neoplastic process.

Adolescent↗

PubMed1998

Transcript levels of aquaporin 1 and carbonic anhydrase IV as predictive indicators for prognosis of renal cell carcinoma patients after nephrectomy.

Since failure of differentiation has been suggested to be involved in the neoplastic process and progression of tumors, we evaluated whether the transcript levels of differentiation markers of proximal renal tubular cells, from which renal cell carcinoma (RCC) arises, could be used as prognostic markers. We used Northern blot analysis to study the expression of aquaporin 1 (aqp1) and carbonic anhydrase IV (ca4) genes in 66 paired samples of primary RCC and non-tumorous kidney tissues. Poor differentiation of tumor cells and non-clear cell-subtype RCC were significantly associated with low levels of aqp1 transcripts. When patients were divided into 2 groups according to level of aqpI transcript in RCC, a low level of aqp1 was significantly associated with unfavorable outcome. Among 18 patients with metastatic RCC and 40 patients with moderately differentiated RCC, those with RCC expressing low levels of aqpl mRNA demonstrated poorer survival than those with RCC expressing relatively high levels of aqp1. Similarly, decreased expression of ca4 mRNA in RCC was associated with poor survival. On multivariate analysis, transcript levels of aqpI and stage of the tumor were the independent factors predicting disease-specific survival. Transcript levels of aqp1 may serve as a new molecular prognostic marker in patients with RCC following nephrectomy.

Aquaporin 1↗

PubMed1998

Clear-cell meningioma: diagnosis by fine-needle aspiration biopsy.

Clear-cell meningiomas have a more aggressive behavior than other meningioma subtypes and the cytologic features of clear-cell meningioma have not been described. A fine-needle aspiration biopsy (FNAB) of a sacral clear-cell meningioma was performed in a 28-yr-old woman. This tumor was a metastasis from a posterior fossa meningioma that had been unresectable, but had been present for 7 yr. Cytologically, clear-cell meningiomas have a whorled, syncytial architecture and spindled to polygonal, bland-appearing nuclei. In contrast to the more classic meningioma, the clear-cell variety has vacuolated cytoplasm. The differential diagnosis includes a number of other neoplastic processes. Separation of clear-cell meningioma from these other entities may be difficult because of its rather unusual cytoplasmic features and its occurrence in unusual sites.

Adult↗

PubMed2000

P53 mutations analysis in benign and malignant breast lesions: using needle rinses from fine-needle aspirations.

The fine-needle aspiration (FNA) technique is a widely used method for diagnostic assessment of breast diseases. In the current study we investigated the feasibility of sampling material for genetic studies from the same FNA samples as would be used for breast cytology. After making smears for cytological examination, the needle was rinsed into phosphate-buffered saline (PBS) solution. The material gained was sufficient for a polymerase chain reaction (PCR)-based study. As the FNA samples reflect a broad range of breast diseases, it is possible to study genetic changes at various stages of the neoplastic process. We looked for mutations in the p53 tumor suppressor gene in 198 FNA needle rinses, 42 from carcinomas and 156 from cytologically benign lesions. In the malignant samples, 22% carried mutations in the p53 gene. We also looked for p53 mutations in matching tissue sections from tumors and found the FNA needle rinses to represent the tumor well. In addition, three mutations in cytologically benign lesions were found, but none of these 3 patients were diagnosed with malignant tumors in the time frame of the study. The clinical significance of p53 mutations in benign breast tissue remains to be determined.

Biopsy, Needle↗

PubMedDate not supplied

The Bethesda system and evaluation of abnormal pap smears.

The Bethesda Pap Smear system and its 1991 revisions aim to simplify Papanicolaou (Pap) smear reporting and make it more reproducible. It redefines the Pap smear request as a medical consultation. The pathologist consultant is required not only to provide the smear reading but also its clinical recommendation. The Bethesda system insists on a detailed Pap smear report assessing specimen adequacy and types of epithelial changes. Squamous cell abnormalities are grouped according to their biologic potential. Both cervical intraepithelial neoplasia, grade I (CIN I) (mild dysplasia) and human papillomavirus (HPV) lesions are grouped together as low-grade squamous intraepithelial lesions (LGSIL), while moderate and severe dysplasia (CIN II and III) belong to the high-grade squamous intraepithelial lesion (HGSIL) category. Atypical squamous cells of undetermined significance (ASCUS) and atypical glandular cells of undetermined significance (AGCUS) need further qualification as to whether they favor either a reactive or neoplastic process. Guidelines for management of abnormal Pap smears are discussed in detail.

Female↗

PubMed1999

Inhibition of tenascin-C expression in mammary epithelial cells by thyroid hormone.

Multiple data suggest a relationship between thyroid hormone (triiodothyronine (T3)) and carcinogenesis. Studies on breast cancer have been inconclusive, suggesting contradictory effects of thyroid status and diseases. Recently, we reported that expression of the extracellular matrix glycoprotein tenascin-C is modulated by T3 during rat brain development. Because tenascin-C has been reported to have growth-, motility-, and angiogenic-promoting activities and to become upregulated during tumorigenesis in breast carcinoma and stromal cells, we analyzed the effects of T3 on tenascin-C expression in mammary epithelial cells. In this study, we showed that tenascin-C RNA expression was inhibited by T3 in normal un-transformed EpH4 mouse mammary epithelial cells expressing appropriate receptors. T3's action appeared to be due to a decreased half-life of the tenascin-C mRNA, with a maximum effect (85% at 100 nM) 48 h after addition. T3 also downregulated tenascin-C in the human mammary tumor cell line SKBR-3, which expresses endogenous thyroid receptors. Immunoprecipitation experiments confirmed that tenascin-C protein content was also decreased by T3 in EpH4 cells (70% reduction at 100 nM). Dexamethasone had a similar inhibitory effect (70% at 100 nM), whereas estradiol, the antiestrogen ICI 164,384, progesterone, and all-trans retinoic acid did not alter tenascin-C expression. Our data demonstrate an inhibitory action of T3 on tenascin-C expression in mammary epithelial cells that may play a role in the physiological regulation of this gene and in neoplastic processes.

Animals↗

PubMed1997

Inflammatory pseudotumor of the trachea in a ten-month-old infant.

Inflammatory pseudotumors occur through a non-neoplastic process that involves abnormal proliferation of spindle cells (myoblasts and fibroblasts) with an inflammatory cell infiltrate. Clinically, radiographically, and grossly these lesions mimic malignant neoplasms but are readily distinguished histologically. We report an infant who presented with an inflammatory pseudotumor of his trachea that caused severe stridor.

Bronchoscopy↗

PubMed2000

Neoplasia of plasma cells with atypical presentation and infection by the human immunodeficiency virus. A presentation of two cases.

Neoplasia of plasma cells acquires special clinical characteristics in patients infected by human immunodeficiency virus (HIV). These patients are much younger at the time of diagnosis, and when they are compared with the general population they show an atypical clinical evolution, with a greater frequency of solitary plasmacytomas, less evidence of a monoclonal plasmatic component, or greater aggressiveness of the neoplastic process. This paper provides the most significant data on two patients infected by HIV and diagnosed for plasma cell neoplasia. Recent pathogenetic hypotheses for plasma cell neoplasias that include immune alterations, chronic viral infections, and hyperexpression of cytokines exist in patients infected by HIV, and this could suggest that this type of neoplasia is another malignant haematological process associated with AIDS.

Adult↗

PubMed1975

Primary granulocytic sarcoma of the small bowel.

A young man developed obstruction of the small bowel due to a neoplastic process, which in retrospect proved to be a primary granulocytic sarcoma, preceding acute granulocytic leukemia for more than 3 years. The histologic, histochemical and ultrastructural findings are presented, together with a review of the literature on granulocytic sarcomas, particularly those presenting as aleukemic forms. It is suggested that these forms may not be so rare and that careful search, using currently available methods, will be rewarding.

Adult↗

PubMed1976

Cytogenetic studies in sideroblastic anemia.

Cytogenetic studies were performed on bone marrow aspirates from seven patients with acquired sideroblastic anemia. In one male patient a 45,X cell line was present in each of three bone marrow aspirates. The remaining six patients had a normal chromosome complement. The abnormal stem line in the bone marrow may be unrelated to the hematologic disorder or may indicate a neoplastic process still latent. The cytogenetic literature on sideroblastic anemia is reviewed.

Aged↗