Review of metanephric adenoma of the kidney with focus on clinical and pathobiological aspects

The concept of metanephric adenoma has become established in recent years. Metanephric adenoma is a rare neoplasm. Macroscopically, the cut surface of the tumor displays a tan to gray or yellow color, and tumors generally form well-circumscribed masses. Histologically, tumors are composed of small epithelial cells that form small acini. Glomeruloid bodies, which are composed of lobulated papillary projections, are occasionally seen. Although there have been few studies using chromosomal analysis, two recent studies have shown partial monosomy or LOH of 2p. On the other hand, the concept of metanephric tumors has recently become broadened. These tumors include metanephric adenomas, adenofibromas and stromal tumors, and they compose a continuous histological spectrum. Therefore, further studies on various aspects are needed to identify the gene responsible for the occurrence of metanephric tumors and, furthermore, to clarify the association among the three types of metanephric tumors.     

Carcinoid tumor of the kidney: case report and review of the literature

Carcinoid tumors are low-grade malignant tumors that arise from neuroendocrine cells. Primary renal carcinoid tumors are extremely uncommon. They seem to be more indolent than renal cell carcinomas, although metastases to regional lymph nodes, liver, and bone have been described. The presence of metastases seems to indicate a more malignant course; however, even with metastases a patient might live for 3 or 4 years. Renal carcinoid tumors should be managed by radical or partial nephrectomy, and good outcomes have been obtained for organ-confined disease after radical excision. Conventional methods of imaging are inadequate for detecting smaller carcinoids, so somatostatin receptor scintigraphy should complement computed tomography and magnetic resonance imaging when searching for occult or metastatic disease. Close follow-up after surgery is necessary.     

Primary neoplasms of the facial nerve

A series of 30 primary facial nerve tumors is reviewed. Most of them were benign (n = 26); there were four malignant tumors. Neoplasms originating within the temporal bone were found to have preoperative facial paralysis in 84 percent of cases; the extracranial tumors had a 35 percent incidence of preoperative facial paralysis. All tumors in this series were treated surgically--by means of a middle fossa or transmastoid approach for the intratemporal group of tumors; the extracranial tumors were removed by the technique of parotid tumor surgery with complete facial nerve dissection. All the patients with preoperative facial weakness required facial nerve transection. Facial paralysis was rehabilitated with nerve grafts, hypoglossal crossover, or muscle transfers. Because "normal" facial expression is still not attainable following repair of complete facial nerve transection, an early diagnosis, hopefully prior to total neurotmesis, is essential. All patients with unexplained facial weakness, especially that which is progressive and persistent, should have the entire course of the facial nerve investigated for the possibility of treatable etiology.     

Morphometry in the differential diagnosis of granulosa-cell tumors of the ovary

Although the diagnosis of granulosa-cell tumors of the ovary is usually consistent and reproducible, in some cases the differentiation from poorly differentiated adenocarcinomas can be difficult. To investigate our subjective impression of the similarity of nuclei in both types of tumors, seven granulosa-cell tumors and eight poorly differentiated adenocarcinomas were studied with morphometry, with a variety of nuclear parameters measured in 100 nuclei per case. The findings showed that, in general, granulosa-cell tumors have a slightly higher mean nuclear contour index (NCI), which is a measure of the nuclear indentation or grooving, and a somewhat lower mean nuclear area than do adenocarcinomas. There is considerable overlap, however, with the nuclear patterns of the two types of tumors forming a morphologic continuum. Multivariate analysis gave a better discrimination but did not entirely eliminate the overlap. The maximum NCI was the best single discriminator. While only one of the granulosa-cell tumors had a maximum NCI less than 5.11, none of the adenocarcinomas exceeded this value. The only granulosa-cell tumor with a maximum NCI below the threshold was in a case with a much less favorable clinical course. The results of this study indicate that objective morphometric nuclear criteria are useful in the diagnosis of granulosa-cell tumors and possibly have some prognostic value.     

Familial posterior fossa brain tumors of infancy secondary to germline mutation of the hSNF5 gene

We have identified a family afflicted over multiple generations with posterior fossa tumors of infancy, including central nervous system (CNS) malignant rhabdoid tumor (a subset of primitive neuroectodermal tumors, or PNET) and choroid plexus carcinoma. Various hereditary tumor syndromes, including Li-Fraumeni syndrome, Gorlin syndrome, and Turcot syndrome, have been linked to increased risk of developing CNS PNETs and choroid plexus tumors. Malignant rhabdoid tumors of the CNS and kidney show loss of heterozygosity at chromosome 22q11. The hSNF5 gene on chromosome 22q11 has recently been identified as a candidate tumor-suppressor gene in sporadic CNS and renal malignant rhabdoid tumors. We describe a family in which both affected and some unaffected family members were found to have a germline splice-site mutation of the hSNF5 gene, leading to exclusion of exon 7 from the mature cDNA and a subsequent frameshift. Tumor tissue shows loss of the wild-type hSNF5 allele, in keeping with a tumor-suppressor gene. These findings suggest that germline mutations in hSNF5 are associated with a novel autosomal dominant syndrome with incomplete penetrance that predisposes to malignant posterior fossa brain tumors in infancy.     

细菌在胃肠道肿瘤发生中的作用及其机制

胃肠道肿瘤具有较高的发病率和死亡率,其防治已成为重要的公共卫生问题。胃肠道内的菌群常参与机体的代谢和免疫反应,协同维持机体的平衡状态。多项研究发现消化道内细菌种类和数目的变化在胃肠道肿瘤的发生和发展中具有重要作用。细菌可通过毒力因子、生物膜、代谢产物等多种因素参与致肿瘤作用,甚至影响化疗药物的疗效,然而,细菌在肿瘤发生中的作用地位尚不明确。因此,本文对细菌致胃肠道肿瘤发生发展的机制进行综述,以期为胃肠道肿瘤的早期防治提供理论依据。     

Computed tomography in the diagnosis of soft tissue neoplasms of the trunk and extremities]

Analysis of CT data on 213 patients with soft tissue and trunk tumors has shown that a majority of malignant and benign tumors have a similar picture (except lipoma). Features of the contours of a tumor and its inner structure do not permit the assessment of its nature. The only significant differential-diagnostic sign of malignant soft tissue tumors is destruction of an adjacent bone, noted in 17.6%. The majority of malignant and benign soft tissue tumors (70.9%) on CT scans look like a single node; recurrent tumors look multinodular (78.2%). Verification of soft tissue tumors, revealed by CT, should be done using morphological methods.     

沉默信息调节因子1在消化系统肿瘤中的作用

沉默信息调节因子1(SIRT1)是Sirtuin 家族中的一员,属于烟酰胺（NAD⁺）依赖的Ⅲ类组蛋白去乙酰化酶,能通过对多种非组蛋白及组蛋白赖氨酸残基进行去乙酰化修饰调节基因表达。近来的研究发现,SIRT1不仅能使肿瘤抑制因子去乙酰化,促进肿瘤发生,还能使肿瘤促进因子去乙酰化,抑制肿瘤发生。SIRT1与肿瘤的生物学特性密切相关,影响肿瘤分期及患者预后。在消化系统肿瘤中,SIRT1具有双面性,既可作为抑癌因子,也可发挥癌因子的作用。近年来,许多研究对SIRT1在肿瘤中的作用靶点及相关信号通路做了深入研究,关于SIRT1在肿瘤中作用机制的新研究不断出现。SIRT1已成为人们攻克肿瘤的一个研究热点。本文通过对SIRT1在肿瘤中的双重作用,尤其是在消化系统肿瘤中的不同作用靶点和参与的信号通路作一综述,希望为临床上治疗消化系统肿瘤提供更有说服力的证据。     

Allelic imbalance in primary breast carcinomas and metastatic tumors of the axillary lymph nodes

Axillary lymph node status is the most important prognostic factor in predicting disease outcome in women with breast cancer. A number of chromosomal aberrations in primary breast tumors have been correlated with lymph node status and clinical outcome, but chromosomal changes particular to metastatic lymph node tumors have not been well studied. DNA samples isolated from laser-microdissected primary breast and metastatic axillary lymph node tumors from 25 women with invasive breast cancer were amplified using 52 microsatellite markers defining 26 chromosomal regions commonly deleted in breast cancer. Levels and patterns of allelic imbalance (AI) within and between breast and lymph node tumors were assessed to identify chromosomal alterations unique to primary or metastatic tumors and to examine the timing of metastatic potential. The overall frequency of AI in primary breast tumors (0.24) was significantly greater (P < 0.001) than that in lymph node tumors (0.10), and congruent AI events were observed for < 20% of informative markers. AI at chromosomes 11q23.3 and 17p13.3 occurred significantly more frequently (P < 0.05) in primary breast tumors alone; no chromosomal regions showed a significantly higher AI frequency in lymph nodes. Higher rates of AI in primary versus metastatic lymph node tumors suggest that acquisition of metastatic potential may be an early event in carcinogenesis, occurring before significant levels of AI accumulate in the primary tumor. In addition, patterns of AI were highly discordant between tumor types, suggesting that additional genetic alterations accumulated independently in the two cell populations.     

Monoclonal antibodies for the treatment of metastases

To investigate critical factors influencing the localization and antitumor effects of monoclonal antibodies (MAb) or toxic conjugates, we have adapted a single rat sarcoma, HSN, for preferential growth in the lungs, liver, and lymph nodes (the major sites of metastasis in humans) and have raised a panel of syngeneic rat MAbs to a stably-expressed cell surface antigen. Using this model we have shown that localization in tumors is significantly influenced by their anatomical location and vascularization, and the degree of MAb interaction with host cells. Uptake in small hepatic tumors was excellent, but access to lung tumors was limited by the poor permeability of pulmonary vessels. HSN cells transfected with the human IL-2 gene and coinjected in low numbers with parental tumors secreted sufficient cytokine to enhance the local permeability of vessels and doubled MAb localization in tumors without any systemic toxicity, suggesting that regional delivery of IL-2 may be used to enhance MAb localization in this situation. In order to extent the applicability of the model to studies of MAbs raised against human tumor targets, we have transfected the human c-erb B-2 gene (homolog of the ratneu) into the highly metastatic HSN.LV subline. MAbs raised against the external domain of the p185 product can now be screened for their ability to localize in metastases, and for various conjugates to inhibit tumor growth either independently of, or in association with, a fully functional immune system.     

Molecular analysis of the chromosome 11p region in renal cell carcinomas.

Comparative histological data suggest that papillary renal cell tumors in adults and Wilms' tumors in children develop from maturation-arrested cells of similar origin. Wilms' tumor is characterized by genetic changes at the chromosome 11p region. In the present study, we have analyzed 10 papillary and 10 non-papillary renal cell tumors and determined the allelic status of 6 loci on the short arm of chromosome 11. Only one papillary renal cell carcinoma among the 20 tumors showed a loss of constitutional heterozygosity for the chromosome 11p region. These data suggest that separate molecular events occur in the development of Wilms' tumor and papillary renal cell tumors, subsequent to the proliferation of maturation-arrested cells of the kidney.     

Common ground in the transcriptional profiles of wounds and tumors

Healing wounds and developing tumors are both sites of dynamic interactions between a variety of cell types. Recent microarray studies comparing wounds and tumors have identified characteristic similarities in gene expression that may prove to be useful for assessing cancer prognosis and for choosing subsequent treatment.     

Soft tissue tumors of the penis: a review

Penile soft tissue tumors comprise 5% of tumors at this site and most have been reported as isolated case reports. The purpose of this review is to aid the practicing surgical pathologist in distinguishing penile soft tissue tumors, such as sarcomatoid squamous cell carcinoma, from other prognostically and therapeutically important entities in the differential diagnosis. Clinical presentation, management, prognosis and factors influencing behavior are reviewed. The immunohistochemical profiles and salient morphologic clues that may help distinguish penile spindle cell tumors from sarcomatoid carcinomas are evaluated. Soft tissue tumors of the penis may be classified as benign or malignant, as superficial or deep and in terms of age at presentation. All are rare. The most common benign soft tissue tumors that affect the penis are vascular neoplasms, followed by tumors of neural, myoid and fibrous origin. Among reported cases, the most frequent malignant penile soft tissue tumors are Kaposi sarcoma and leiomyosarcoma. Correctly diagnosing penile soft tissue tumors is imperative, because the biologic behavior and the clinical management of these neoplasms vary considerably. Distinguishing sarcomas from sarcomatoid carcinoma and melanoma is particularly important. Accurate diagnosis is best facilitated by consideration of all available aspects of the case, including clinical information, histopathologic findings and immunohistochemical results.     

Synchronous tumors of the female genital tract: triple malignant and one benign tumor

Synchronous tumors of the female genital tract are rare, accounting for 0.7-1.8% of all cases. Double synchronous tumors are most often mentioned in the literature. Reviewing the English literature on this topic, we have found only one case report of a triple synchronous tumor. The 55-year-old patient mentioned in our case has had advanced diabetes mellitus, and has been treated with corticosteroid therapy for a long time because of chronic obstructive pulmonary disease (COPD). She was examined because of her vulvar tumor. During the diagnostic procedure, cervical and endometrial malignant tumors and a benign ovarian cyst have also been found. This event brings to our attention the fact that we should be prepared to manage synchronous even triple malignant gynecological tumors.     

Allele-specific hypermethylation of the retinoblastoma tumor-suppressor gene.

Inactivation of the retinoblastoma gene appears to have a fundamental role in the genesis of retinoblastoma, osteosarcoma, and other malignant tumors. The gene is generally inactivated because of loss-of-function mutations, although epigenetic phenomena, such as hypermethylation of the promoter region, could possibly have the same effect. We investigated the methylation pattern at the 5' end of the retinoblastoma gene, including its promoter region and exon 1, in DNA purified from 56 primary retinoblastomas. We found five tumors with evidence for hypermethylation, all from unilateral, simplex patients. No methylation abnormalities were detected in DNA purified from the leukocytes from these patients. It is interesting that in one of these tumors the hypermethylation was confined to one allele. There were no mutations in a 1,306-bp sequence including the hypermethylated region that might account for the allele-specific hypermethylation. We believe that the hypermethylation of the retinoblastoma gene that we found in these tumors corresponds to the allelic inactivation of the gene, and we speculate that erroneous hypermethylation without alteration of nucleotide sequence occasionally plays a role in the genesis of this cancer. If this is true, then retinoblastomas with hypermethylation might be treatable with chemotherapeutic agents that interfere with methylation of DNA.     

Cell-autonomous cytokinin-independent growth of tobacco cells transformed by Agrobacterium tumefaciens strains lacking the cytokinin biosynthesis gene.

Mutations at the cytokinin biosynthesis locus (tmr) of Agrobacterium tumefaciens usually result in strains that induce tumors exhibiting the rooty phenotype associated with high auxin-to-cytokinin ratios. However, tobacco (Nicotiana tabacum cv Havana 425) leaf disc explants responded to tmr- mutant strain A356 by producing rapidly growing, unorganized tumors, indicating that these lines can grow in a cytokinin-independent fashion despite the absence of a functional tmr gene. Several methods have been used to characterize the physiological and cellular basis of this phenotype. The results indicate that tmr- tumors have a physiologically distinct mechanism for cytokinin-independent growth in comparison to tumors induced by wild-type bacteria. The cytokinin-independent phenotype of the tmr- transformants appears to be cell autonomous in nature: only the transformed cells and their progeny were capable of cytokinin-independent growth. Specifically, the tmr- tumors did not accumulate cytokinin, and clonal analysis indicated the tmr- transformed cells were not capable of stimulating the growth of neighboring nontransformed cells. Finally, the cytokinin-independent phenotype of the tmr- transformants was shown to be cold sensitive, whereas the wild-type tumors exhibited a cold-resistant cytokinin-independent phenotype. Potential mechanisms for this novel form of cytokinin-independent growth, including the role of the dehydrodiconiferyl alcohol glucosides found in both tumor types, are discussed.     

Biological and clinical review of stromal tumors in the gastrointestinal tract

Submucosal tumors of the gastrointestinal tract (GI tract) mainly consist of gastrointestinal mesenchymal tumors (GIMTs) that are distributed in the GI tract from the esophagus through the rectum. GIMTs include myogenic tumors, neurogenic tumors and gastrointestinal stromal tumors (GISTs). The term "GIST" is now preferentially used for the tumors that express CD34 and KIT. GIMTs are composed of spindle or epithelioid cells, and 20% to 30% show malignant behavior, including peritoneal dissemination and hematogenous metastasis. KIT expression and mutations in the c-kit gene are found only in GISTs, but not in myogenic or neurogenic tumors. Mutation in the c-kit gene is associated with aggressive features and poor prognosis, and malignant GISTs frequently have mutations in the c-kit gene. The clinicopathological features of GISTs with or without c-kit mutations are markedly different. Therefore, GIMTs may be divided into four major categories based on histochemical and genetic data: myogenic tumors; neurogenic tumors; GISTs with c-kit mutation; and GISTs without c-kit mutation. The origin of GISTs is not fully understood. However, phenotypical resemblance to the interstitial cells of Cajal (ICCs) and gain-of-function mutations in the c-kit gene may suggest origin from ICCs and/or multipotential mesenchymal cells that differentiate into ICCs.     

nm23-H1调控肿瘤侵袭转移分子机制研究进展

侵袭转移是恶性肿瘤的重要生物学特征,也是导致肿瘤患者治疗失败和死亡的主要原因。研究表明,nm23基因家族与肿瘤的发生、发展及转移密切相关。其中,nm23-H1是被发现的第一个人类nm23基因,与肿瘤侵袭转移关系极为密切。现将nm23-H1基因调控肿瘤侵袭转移分子机制的研究进展作一综述。     

Myogenic cell proliferation and generation of a reversible tumorigenic phenotype are triggered by preirradiation of the recipient site

Environmental influences have profound yet reversible effects on the behavior of resident cells. Earlier data have indicated that the amount of muscle formed from implanted myogenic cells is greatly augmented by prior irradiation (18 Gy) of the host mouse muscle. Here we confirm this phenomenon, showing that it varies between host mouse strains. However, it is unclear whether it is due to secretion of proliferative factors or reduction of antiproliferative agents. To investigate this further, we have exploited the observation that the immortal myogenic C2 C12 cell line forms tumors far more rapidly in irradiated than in nonirradiated host muscle. We show that the effect of preirradiation on tumor formation is persistent and dose dependent. However, C2 C12 cells are not irreversibly compelled to form undifferentiated tumor cells by the irradiated muscle environment and are still capable of forming large amounts of muscle when reimplanted into a nonirradiated muscle. In a clonal analysis of this effect, we discovered that C2 C12 cells have a bimodal propensity to form tumors; some clones form no tumors even after extensive periods in irradiated graft sites, whereas others rapidly form extensive tumors. This illustrates the subtle interplay between the phenotype of implanted cells and the factors in the muscle environment.