卵巢非特异性类固醇细胞瘤临床病理分析

目的探讨卵巢非特异性类固醇细胞瘤的临床、病理学特征以及诊断、治疗。方法对8例卵巢非特异性类固醇细胞瘤进行HE和免疫组织化学（EliVision法）染色及特殊染色,结合临床资料和文献进行分析。结果7例良性非特异性类固醇肿瘤,肿瘤主要由两种细胞构成：一种为多角形细胞,胞质含小颗粒或嗜酸性;一种为胞质含空泡的较大细胞。细胞排列成巢或条索状,似肾上腺球状带和束状带。1例恶性非特异性类固醇肿瘤,细胞呈明显异型性,核分裂象7／10 HPF,伴出血、坏死。免疫组织化学显示：肿瘤细胞胞质内钙结合蛋白和α-抑制素普遍阳性表达。诊断非特异性类固醇细胞瘤需与广泛黄素化的颗粒细胞瘤、卵泡膜细胞瘤、富于脂质的支持细胞瘤和嗜酸型透明细胞癌等相鉴别。良性肿瘤治疗一般为肿瘤切除或加患侧附件切除术;恶性肿瘤行肿瘤加附件切除,辅以化疗或促性腺激素激动剂治疗。结论非特异性类固醇细胞瘤是类固醇细胞肿瘤中最常见的类型,良性多见;免疫组织化学可辅助肿瘤诊断;治疗方法主要取决于肿瘤的良恶性。     

Bilateral Sertoli cell tumors of the testis—a likely new extracolonic manifestation of familial adenomatous polyposis

Testicular Sertoli cell tumors are rare and usually sporadic and unifocal. The large cell calcifying Sertoli cell tumor variant is known to be associated with Carney and Peutz?CJeghers syndromes and can be bilateral in these patient populations. There has been no documented association of Sertoli cell tumor with familial adenomatous polyposis (FAP) in the literature. The case presented is a bilateral Sertoli cell tumor occurring in a 34-year-old patient with FAP. The tumor had a conventional Sertoli cell tumor morphology, but with different morphology in the left and right sites. Beta-catenin immunostain showed strong nuclear reactivity in the tumor cells but not the nonneoplastic Sertoli cells. The presence of bilaterality as well as overexpression of beta-catenin by this tumor supports an association of the development of Sertoli cell tumor with the patient??s FAP syndrome and adenomatous polyposis coli inactivation.     

血管内皮细胞在肿瘤侵袭微生态系统中作用的研究进展

目的介绍血管内皮细胞在肿瘤侵袭微生态系统中的作用及研究进展。方法系统复习肿瘤侵袭微生态系统研究的背景、组成要素、与肿瘤微环境的区别及血管内皮细胞对其影响的相关文献,并予以归纳总结。结果肿瘤侵袭微生态系统是指肿瘤侵袭过程的细胞群落与其栖息宿主环境所构成的一个自然的整体功能系统,属于细胞和分子水平的生态系统,它包括肿瘤细胞本身在内,具有生态系统的规律;而肿瘤的微环境则与肿瘤侵袭微生态系统不同,它是肿瘤细胞赖以生存的所有外界条件的总称,是一种结构体系,不包括肿瘤细胞本身,不具有生态系统的规律。肿瘤侵袭微生态系统组成要素包括肿瘤细胞群落和宿主细胞群落以及它们的栖息环境(基质成分),而血管内皮细胞群落是最主要的宿主细胞群落,其对肿瘤侵袭微生态系统的作用主要表现在肿瘤细胞群落和内皮细胞群落之间的营养联系上,这种营养联系形成了肿瘤微生态系统的物质循环,包括营养循环和细胞基质循环。肿瘤侵袭转移是肿瘤细胞群落和血管内皮细胞群落不断重建营养联系的结果。结论血管内皮细胞通过和肿瘤细胞之间的营养联系对肿瘤侵袭微生态系统进行调控,切断肿瘤细胞群落和血管内皮细胞群落之间的营养联系是肿瘤治疗的关键。     

Aquaporins—new players in cancer biology

The aquaporins (AQPs) are small, integral-membrane proteins that selectively transport water across cell plasma membranes. A subset of AQPs, the aquaglyceroporins, also transport glycerol. AQPs are strongly expressed in tumor cells of different origins, particularly aggressive tumors. Recent discoveries of AQP involvement in cell migration and proliferation suggest that AQPs play key roles in tumor biology. AQP1 is ubiquitously expressed in tumor vascular endothelium, and AQP1-null mice show defective tumor angiogenesis resulting from impaired endothelial cell migration. AQP-expressing cancer cells show enhanced migration in vitro and greater local tumor invasion, tumor cell extravasation, and metastases in vivo. AQP-dependent cell migration may involve AQP-facilitated water influx into lamellipodia at the front edge of migrating cells. The aquaglyceroporin AQP3, which is found in normal epidermis and becomes upregulated in basal cell carcinoma, facilitates cell proliferation in different cell types. Remarkably, AQP3-null mice are resistant to skin tumorigenesis by a mechanism that may involve reduced tumor cell glycerol metabolism and ATP generation. Together, the data suggest that AQP expression in tumor cells and tumor vessels facilitates tumor growth and spread, suggesting AQP inhibition as a novel antitumor therapy.     

PHAGOCYTOSIS OF LYMPHOBLASTOID CELLS AND CELL DESTRUCTION OF HUMAN MALIGNANT TUMOR CELLS

On the basis of the previous study^8,9 on the cell interaction between malignant tumor cells and other cells, especially with lymphocytes, the present study was carried out by investigating cell to cell interaction of human malignant tumor cells and human lymphoblastoid cells such as T-cell (MOLT-4 cell) and B-cell (Burkftt lymphoma cell).
As a result it has been revealed that live lymphoblastoid cells were not adhered on the cell surface of the tumor cells, nor is it ingested by tumor cells, but in the presence of HVJ (Sendai virus: 2,000 H.A. Units) it adheres slightly on the cell surface of tumor cell but no cell fusion of tumor cells and lymphoblastoid cells is observable. On the other hand, the tumor cell as well as T-cell and B-cell all have receptors to concanavah A (Con.A) on their cell surfaces, and they show a marked cell binding such as tumor cell and T-cell, tumor cell and B-cell, and there can be observed a marked phagocytosis of lymphoblastoid cells by tumor cells. Moreover, the tumor cells that have phagocythd lymphoblastoid cells undergo a marked cell destruction within 4 hours of cell-binding and phagocytosis, which is especially prominent in the case of phagocytosis of E.B cell by tumor cell.     

肿瘤疫苗治疗膀胱癌进展

肿瘤疫苗免疫治疗是利用肿瘤抗原进行主动免疫来激发、增强机体的主动特异性免疫反应.肿瘤疫苗的设计,首先是基于对肿瘤发生免疫逃逸机理的认识.肿瘤免疫逃逸机制十分复杂,缺乏抗原表位、MHC表达下调以及共刺激分子或某些粘附分子的缺乏等可能是其重要的机理.肿瘤疫苗策略包括基因疫苗、肽和蛋白疫苗、基因修饰的肿瘤细胞疫苗以及抗独特型抗体疫苗等.利用DC细胞荷载抗原肽或者基因修饰的肿瘤细胞等建立膀胱癌细胞疫苗,在体内、外实验中已证实对膀胱癌的治疗有一定的效果.     

Modulating malignant epithelial tumor cell adhesion,migration and mechanics with nanorod surfaces

The failure of tumor stents used for palliative therapy is due in part to the adhesion of tumor cells to the stent surface. It is therefore desirable to develop approaches to weaken the adhesion of malignant tumor cells to surfaces. We have previously developed SiO₂ coated nanorods that resist the adhesion of normal endothelial cells and fibroblasts. The adhesion mechanisms in malignant tumor cells are significantly altered from normal cells; therefore, it is unclear if nanorods can similarly resist tumor cell adhesion. In this study, we show that the morphology of tumor epithelial cells cultured on nanorods is rounded compared to flat surfaces and associated with decreased cellular stiffness and non-muscle myosin II phosphorylation. Tumor cell viability and proliferation was unchanged on nanorods. Adherent cell numbers were significantly decreased while single tumor cell motility was increased on nanorods compared to flat surfaces. Together, these results suggest that nanorods can be used to weaken malignant tumor cell adhesion, and therefore potentially improve tumor stent performance.     

Gonadal tumor with granulosa cell tumor features in an adult testis

Granulosa cell tumor is almost exclusively an ovarian tumor. Rare cases of granulosa cell tumor have been reported involving the testes. We report a testicular gonadal stromal tumor with granulosa cell differentiation in a 54-year-old white man. The tumor was discovered by an ultrasound evaluation for left hydrocele. The patient was clinically asymptomatic. On frozen section, the initial impression was a malignant lymphoma. Final histology on the orchiectomy specimen showed a gonadal stromal tumor with granulosa cell features. Immunohistochemical studies excluded malignant lymphoma and germ cell tumors, consistent with a stromal tumor. This case report illustrates the challenges for the pathologist in making an accurate diagnosis in unusual testicular tumors.     

移植性鳞癌兔模型的建立及生物学特征

背景：兔VX2荷瘤目前已广泛应用于全身多个器官肿瘤动物模型的建立,但在耳郭建立鳞癌动物模型至今少有报道。 目的：采用2种不同移植瘤方法建立稳定的兔耳VX2移植瘤模型,并对所建肿瘤模型的生物学特性进行观察和比较。 方法：将新西兰大白兔分别用瘤细胞悬液注入法和瘤组织块切开植入法移植于兔耳皮下,观察和比较 2种方法所建立的模型的肿瘤生长状况、成瘤率和自发转移发生率。 结果与结论：瘤细胞悬液注入组和瘤组织块植入组的成瘤率分别为73.3%和50%,差异有显著性意义(P < 0.05)。局部淋巴结转移率分别为75%和86%。两种方法建立的兔VX2鳞癌移植瘤模型中,组织呈浸润性生长,瘤细胞核深染,分裂相多见,并呈癌巢排列的符合鳞状细胞癌特征。证实,瘤细胞悬液注入法和瘤组织块切开植入法建立的移植瘤模型均较接近人鳞癌自然生长过程。瘤细胞悬液注入法建立的动物模型,因成瘤率和转移率高,更适合于鳞癌研究。     

Combined tall cell carcinoma and Hürthle cell carcinoma (collision tumor) of the thyroid

Tall cell carcinoma and Hürthle cell carcinoma are 2 aggressive forms of differentiated follicular-derived thyroid carcinomas. We present a case where these malignant tumors of thyroid coexisted. The tumor originated in the thyroid as a mixed tumor and metastasized as a tall cell tumor to the lymph nodes and as a Hürthle cell carcinoma to lungs. The coexistence of these tumor types is rare and sheds light on the histogenesis of Hürthle cell tumors and the metastatic behavior of combined tumors.     

A combined neurofibroma-granular cell tumor of the middle cranial fossa.

A case of a combined neurofibroma-granular cell tumor in a 52 years old gunsmith is presented. The tumor developed after an intracranial trigeminal nerve operation 25 years previously. The solid tumor in the left middle cranial fossa had displaced and infiltrated the temporal lobe. It had expanded via the optic nerve into the left orbit, and further the apex partis petrosae was destroyed. The neurofibroma part shows histological aspects of malignancy, the granular cell tumor, considering its infiltrating and destructive growth, may be regarded as malignant as well. In intermingling portions of the tumor, transitional types of fiber-like and granular cells are prominent. In the peripheral zone of the tumor apparently reactively proliferated polynuclear astrocytes are seen with occasionally intracytoplasmatic lymphocytes (emperipolesis?). A short review of the literature and the theories concerning the histogenesis of the granular cell tumor is given. Whereas most authors in recent years suggest a Schwann cell origin, based on electron microscopic findings, this intermediate tumor type motivates us to postulate a mesodermal origin of the granular cell tumor. The question of viral influence is discussed briefly.     

Giant cell tumor of bone express p63.

p63 contributes to skeletal development and tumor formation; however, little is known regarding its activity in the context of bone and soft tissue neoplasms. The purpose of this study was to investigate p63 expression in giant cell tumor of bone and to determine whether it can be used to discriminate between other giant cell-rich tumors. Seventeen cases of giant cell tumor of bone were examined to determine the cell type expressing p63 and identify the isoforms present. Total RNA or cell protein was extracted from mononuclear- or giant cell-enriched fractions or intact giant cell tumor of bone and examined by RT-PCR or western blot, respectively. Immunohistochemistry was used to evaluate p63 expression in paraffin embedded sections of giant cell tumor of bone and in tumors containing multinucleated giant cells, including: giant cell tumor of tendon sheath, pigmented villonodular synovitis, aneurysmal bone cyst, chondroblastoma, and central giant cell granuloma. The mononuclear cell component in all cases of giant cell tumor of bone was found to express all forms of TAp63 (alpha, beta, and gamma), whereas only low levels of the TAp63 alpha and beta isoforms were detected in multinucleated cells; DeltaNp63 was not detected in these tumors. Western blot analysis identified p63 protein as being predominately localized to mononuclear cells compared to giant cells. This was confirmed by immunohistochemical staining of paraffin-embedded tumor sections, with expression identified in all cases of giant cell tumor of bone. Only a proportion of cases of aneurysmal bone cyst and chondroblastoma showed p63 immunoreactivity whereas it was not detected in central giant cell granuloma, giant cell tumor of tendon sheath, or pigmented villonodular synovitis. The differential expression of p63 in giant cell tumor of bone and central giant cell granuloma suggest that these two tumors may have a different pathogenesis. Moreover, p63 may be a useful biomarker to differentiate giant cell tumor of bone from central giant cell granuloma and other giant cell-rich tumors, such as giant cell tumor of tendon sheath and pigmented villonodular synovitis.     

Survey of neuropeptide gene expression in tumor cell lines.

The presence of 3 different neuropeptide mRNAs with a strict cell-specific expression in vivo was investigated in 13 tumor cell lines from neuroendocrine and in 23 tumor cell lines from non-neuroendocrine origin. Northern blots showed no expression of mRNA for vasopressin (VP) in the 36 tested cell lines. Very low oxytocin (OT) mRNA hybridization signals were detected in the rat pituitary tumor cell line GH4C2 and the rat pancreas tumor cell line RIN5. Both the rat pituitary tumor cell line AtT-20 and the human myeloid leukemia cell line K562, contained proopiomelanocortin (POMC) mRNA. The low incidence of VP, OT and POMC gene expression in the tested tumor cell lines was not influenced by treatments inducing differentiation. In contrast, the cholecystokinin (CCK) gene which is widely present in nervous and endocrine systems was abundantly expressed in the human primitive neuroepithelioma cell line SK-N-MC and its clonal derivative SK-N-MC-IX-C. The results indicate that the expression of neuropeptide genes is very rare in tumor cell lines. The lack of expression in undifferentiated cells agrees with the appearance of expression after day 13 of the embryogenesis when maturation of neurons begins.     

Large cell calcifying Sertoli cell tumor of the testis: comparative immunohistochemical study with Leydig cell tumor

Large cell calcifying Sertoli cell tumor is a rare type of testicular tumor. Reported herein is a Japanese patient with this tumor not associated with Carney's complex. An 11-year-old boy was admitted to hospital because of left testicular enlargement, and radical orchiectomy was performed. Macroscopically, the tumor was well circumscribed and had a maximum diameter of approximately 2 cm. The cut surface showed a yellow-white solid mass. Histologically, the tumor was composed of large neoplastic cells with abundant eosinophilic cytoplasm with a tubular, trabecular, and solid arrangement and loose myxoid stroma with irregularly shaped calcification. Immunohistochemically, the tumor cells were positive for vimentin, S-100 protein, calretinin, inhibin-alpha, melan-A, and CD10, and type IV collagen and laminin were observed in the extracellular matrix around the tumor cells. The distributions of melan-A, CD10, and mitochondria were characteristically patchy; in contrast, they were diffusely distributed in the cytoplasm in a control case of Leydig cell tumor. The differences in immunostaining patterns for melan-A, CD10, and mitochondria as well as positivity for S-100 protein-beta might be useful diagnostic hallmarks of large cell calcifying Sertoli cell tumor for discrimination from Leydig cell tumor.     

Ovarian serous cystadenoma associated with Sertoli-Leydig cell tumor--a case report.

We Describe a case of ovarian serous cystadenoma having Sertoli-Leydig cell tumor, well differentiated, in the cystic septum. Well differentiated Sertoli-Leydig cell tumor coexisting with other tumor, including serous tumor, has not yet been described. In all cases of Sertoli-Leydig cell tumor with heterologous components or other tumors, the androblastomatous components are intermediately or poorly differentiated. The present case revealed a well differentiated Sertoli-Leydig cell tumor arising in a septum of serous cystadenoma, as a circumscribed nodule. With these findings, we discuss the possibility of this Sertoli-Leydig cell tumor, considered a mural nodule, which is well established in cystic common epithelial tumors of the ovary.     

Endothelial cells expressing Bcl-2 promotes tumor metastasis by enhancing tumor angiogenesis, blood vessel leakiness and tumor invasion

Metastatic spread of tumor cells to vital organs is the major cause of mortality in cancer patients. Bcl-2, a key antiapoptotic protein, is expressed at high levels in a number of human tumors. We have recently shown that Bcl-2 is also overexpressed in tumor-associated blood vessels in head-and-neck cancer patients. Interestingly, enhanced Bcl-2 expression in tumor blood vessels is directly correlated with metastatic status of these cancer patients. In addition, endothelial cells (ECs) expressing Bcl-2 showed increased production of interleukin-8 (IL-8) resulting in significantly enhanced tumor cell proliferation and tumor cell invasion. Therefore, we hypothesized that Bcl-2 expression in tumor-associated ECs may promote tumor metastasis by enhancing tumor cell invasiveness and release in the circulation. To test our hypothesis, we coimplanted tumor cells along with ECs expressing Bcl-2 (EC-Bcl-2) in the flanks of SCID mice. Our results demonstrate that incorporation of EC-Bcl-2 in primary tumors significantly enhanced tumor cell metastasis to lungs and this EC-Bcl-2-mediated tumor metastasis was independent of primary tumor size. In addition, Bcl-2-mediated tumor metastasis directly correlated with increased tumor angiogenesis. Bcl-2 expression in ECs also promoted transendothelial cell permeability, blood vessel leakiness and tumor cell invasion. EC-Bcl-2-mediated tumor cell proliferation and tumor cell invasion were significantly mediated by IL-8. These results suggest that Bcl-2, when expressed at higher levels in tumor-associated ECs, may promote tumor metastasis by enhancing tumor angiogenesis, blood vessel leakiness and tumor cell invasiveness.     

Patterns of cellular proliferation in normal and tumor cell populations.

Three types of cell mosaics have been used in mammalian studies: hemopoietic shimeras, mosaics formed by aggregation of preimplatation embryos, and mosaics resulting from X-chromosome inactivation. The problems investigated with these cell mosaics have included normal tissue orgaization, cell selection, primordial cell pool sizes, and tumor cell kinetics. The emphasis in this review is on the application of X-chromosome inactivation mosaics to the analysis of tumor cell proliferation. The first application of mosaicism to tumor ontogeny involved leiomyomas and demonstrated single cell and independent origin of the tumors. Other tumor studies are reviewed including those of presumed multiple cell origin, especially those of hereditary origin and viral etiology. The concept of target size is invoked to explain these multiple cell origin tumors. The recent reports on the clonal nature of atherosclerotic plaques is also discussed. Emphasis is placed on resolving the relationship between the multiclonal underlying fatty streak and the clonal plaque in order to understand the implications of the clonal plaques.     

Clear Cell "Sugar" Tumor of the Lung: A Well-Enhanced Mass with an Early Washout Pattern on Dynamic Contrast-Enhanced Computed Tomography

Clear cell tumor of the lung is a rare and very unusual benign pulmonary tumor. As clear cell tumor of the lung contains abundant cytoplasmic glycogen, this tumor is called "sugar tumor". We report a case of sugar tumor in a 64-yr-old man presenting as a round pulmonary nodule. On dynamic computed tomography (CT) scans, the solitary pulmonary nodule showed early wash-in enhancement with an early washout pattern like a lung malignancy. The patient underwent wedge resection for the tumor. Pathologic examination, including immunohistochemical studies, revealed that the nodule was a benign clear cell tumor, so-called "sugar tumor". Because only a small number of cases have been reported previously, clinical aspects, radiological characteristics on dynamic contrast-enhanced CT, and differential diagnosis of the tumor are not well established. Herein we present a clear cell tumor of the lung and discuss the clinical, radiological, and pathological features of the tumor.     

Expression of gamma-subunit of enolase, neuron-specific enolase, in human non-neuroendocrine tumors and derived cell lines

The gamma-subunit of 2-phospho-D-glycerate hydrolyase, E.C. 4.2.1.11 (enolase), neuron-specific enolase (NSE), is present at high concentrations in neurons and neuroendocrine cells and has therefore recently been introduced as a marker for neuroendocrine tumors. By the indirect methods, immunocytochemistry and radioimmunoassay, NSE has been detected also in some nonneuroendocrine tumors, a finding that could reflect technical artifacts or the capacity for NSE expression in nonneuroendocrine tumor cells. This paper reports on the expression of NSE in human neuroendocrine and nonneuroendocrine tumor specimens and in a panel of permanent human cell lines, by using a direct (enzymatic) and an indirect (radioimmunoassay) method for determination of NSE. We detected NSE in all tested tumor specimens and neuroendocrine tumor cell lines and in a majority (21 of 24) of the nonneuroendocrine tumor cell lines. In general, neuroendocrine tumor specimens and derived tumor cell lines contained more NSE than the nonneuroendocrine tumor specimens and cell lines. However, some of the cultured hematopoietic cell lines (T leukemia and Epstein-Barr virus immortalized B lymphoblastoid cell lines) had NSE levels comparable to those found in some neuroblastoma and small-cell lung carcinoma cell lines. We conclude that NSE is not exclusively expressed in neuroendocrine tumor cells.