The significance of atypia within teratomatous metastases after chemotherapy for malignant germ cell tumors

The completely resected teratomatous metastases of 55 patients who had been treated with cisplatin-based combination chemotherapy for non-seminomatous germ cell tumors were reviewed to see if cellular atypia had an effect with respect to recurrent disease. The degree of atypia of the epithelial and mesenchymal elements was assessed on the basis of the cytologic features and mitotic activity. Twenty-three percent of the cases contained high-grade epithelial elements, whereas high-grade mesenchymal elements occurred in 18% of the cases; in addition there were nine cases classified as showing frankly malignant teratomatous elements. The presence of cytologically disturbing epithelial and mesenchymal elements (which, however, lacked an invasive malignant pattern) correlated with an increased incidence of recurrent teratoma compared to less atypical teratomatous elements (23% vs. 6% for epithelial elements, and 18% vs. 9% for mesenchymal elements, respectively). This difference, however, was not statistically significant (P greater than 0.05). There was no correlation between teratomatous atypia and recurrent, non-teratomatous germ cell tumor. The presence of an invasive malignant pattern did identify patients at significantly increased risk for recurrent teratoma-derived tumor. The authors conclude that cytologic atypia in the absence of invasion is not sufficient justification for altering the usual therapeutic strategies for patients with teratomatous metastases.     

An autopsied case of pulmonary blastoma with high serum alpha-fetoprotein and carcinoembryonic antigen levels

A 75-year-old male case of a pulmonary blastoma with high serum alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) levels is reported. A mass shadow in the right lower lung field was visible on examination of a chest X-ray. Serum AFP and CEA levels were 466.1 ng/ml and 5.8 ng/ml, respectively. The autopsy revealed a pulmonary blastoma composed of malignant epithelial and mesenchymal elements. In the epithelial elements, AFP and CEA producing tumor cells were detected by immunoenzymatic labelling (PAP) methods.     

上皮-间质转化在非小细胞肺癌侵袭与转移中作用的研究进展

上皮-间质转化（Epithelial—mesenchymal transition,EMT）与恶性肿瘤的侵袭及转移有着密切的关系,是目前研究恶性肿瘤侵袭及转移的热点。有大量研究表明在多种恶性肿瘤如乳腺癌、卵巢癌和非小细胞肺癌的侵袭与转移过程中都有上皮-间质转化现象,并阐述上皮-间质转化的信号通路及其蛋白分子。本文对上皮-间质转化在非小细胞肺癌侵袭与转移的研究成果做一综述。     

Malignant pediatric brain tumor of primitive small round cell proliferation with bland-looking mesenchymal spindle cell elements

It is often difficult to classify rare malignant pediatric mixed brain tumors composed of mesenchymal elements. A 6-year-old boy presented to our hospital with a left frontal massive tumor manifesting as complaints of rapidly progressive right hemiparesis and motor aphasia over 2 weeks. Computed tomography showed a left frontal mass with thick calcification. Magnetic resonance imaging revealed an enhanced lesion with perifocal edema and mass effect. Total removal of the tumor was performed. Histological examination of the resected tumor revealed an anaplastic malignant small round cell component with a bland-looking mesenchymal spindle cell component. The patient was treated with irradiation to the whole craniospinal axis and a boost to the tumor bed, followed by chemotherapy consisting of ifosfamide, cisplatin, and etoposide, resulting in good control without local recurrence or metastasis at 2 years. A combined malignant tumor composed of ectodermal and mesenchymal components is generally named malignant ectomesenchymoma (MEM). The more malignant part of MEM is the mesenchymal component in most cases. In the present case, the more malignant component was not the mesenchymal component, but the small round cells.     

Sarcomatoid carcinoma of the stomach. A report of three cases with immunohistochemical and ultrastructural observations

The authors report three cases of sarcomatoid carcinoma arising in the stomach. This uncommon tumor is characterized by a mixture of malignant epithelial and spindle cell elements. All three tumors were large (average diameter, 5 cm) and infiltrated deep into the stomach wall. Two of the tumors had a polypoid configuration; the third was ulcerated and endophytic. Intestinal metaplasia was present adjacent to the tumor in all cases, with dysplasia in two. Immunohistochemical studies showed positivity for cytokeratin, carcinoembryonic antigen, and epithelial membrane antigen in the epithelial component of all tumors, and Leu-M1 was positive in the epithelial component of one. The spindle cell components contained vimentin, and in tumor 2, the spindle cell component was also positive for desmin. Two tumors showed focal positivity for cytokeratin in the spindle cells immediately adjacent to the epithelial component. Ultrastructurally, the spindle cell component of two tumors was composed of undifferentiated cells without specific epithelial or mesenchymal features. The third tumor contained occasional cells with features of myofibroblasts.     

肝肉瘤样癌1例并文献复习

目的：探讨肝肉瘤样癌患者的临床及病理学特征、诊断、鉴别诊断、治疗和预后。方法：结合我院收治的肝肉瘤样癌1例临床资料,分析国内外文献报道的该病临床特点、影像学表现、病理学特点,治疗和预后。结果：大部分该病患者均有腹痛和发热的临床表现,病理学上肿瘤都包含明确的恶性上皮性成分和梭形细胞肉瘤样成分且上皮和间叶性两种标记物表达阳性,愈后差。结论：肝肉瘤样癌是一种罕见的恶性肿瘤,恶性程度高,浸润性强,病因不明,目前无有效治疗,预后很差。     

Inflammatory myofibroblastic tumor of the larynx with anaplastic lymphoma kinase (ALK) protein overexpression. A case report

Inflammatory myofibroblastic tumor is an uncommon lesion which mainly develops in the lung and is extremely rare in the larynx. It may be easily misinterpreted as a malignant epithelial or mesenchymal spindle cell neoplasm. Histological and clinical knowledge of this lesion is important to exclude misdiagnosis and inappropriate treatment. We report a case of inflammatory myofibroblastic tumor arising on the right vocal cord of a 23-year-old man. The tumor was composed of a mixture of spindle cells and inflammatory elements. Immunohistochemical investigation revealed that the neoplastic cells expressed anaplastic lymphoma kinase (ALK) protein.     

Salivary gland carcinosarcoma: oligonucleotide array CGH reveals similar genomic profiles in epithelial and mesenchymal components

In this study, we present a case of parotid gland de novo carcinosarcoma. Salivary gland carcinosarcoma (or true malignant mixed tumor) is a rare biphasic neoplasm, composed of both malignant epithelial and malignant mesenchymal components. It is yet unclear whether these two phenotypes occur by collision of two independent tumors or if they are of clonal origin. To analyze the clonality of the different morphologic tumor components, oligonucleotide microarray-based comparative genomic hybridization (oaCGH) was performed on the carcinoma and the sarcoma entity separately. This technique enables a high-resolution, genome-wide overview of the chromosomal alterations in the distinct tumor elements. Analysis of both fractions showed a high number of DNA copy number changes. Losses were more prevalent than gains (82 and 49, respectively). The carcinomatous element displayed more chromosomal aberrations than the sarcomatous component. Specific amplifications of MUC20 (in mesenchymal element) and BMI-1 (in both elements) loci were observed. Overall homology between the two genomic profiles was 75%. DNA copy number profiles of the epithelial and mesenchymal components in this salivary gland carcinosarcoma displayed extensive overlap, indicating a monoclonal origin. Since losses are shared to a larger extent than gains, they seem to be more essential for initial oncogenic events. Furthermore, specific amplifications of a mucin and a Polycomb group gene imply these proteins in the tumorigenesis of carcinosarcomas.     

Localized primary tumors of the pleura: an analysis of 40 cases.

A study of 40 localized primary tumors of the pleura in the files of the Canadian Tumour Reference Centre revealed a considerable diversity in their histologic structure. Collagenized, hemangiopericytoma-like and cellular areas were the main forms of growth pattern, with half of the tumors showing a mixture of two or more of these elements. Inclusions of non-neoplastic bronchioloalveolar epithelium were frequently seen in areas of tumor adjacent to lung substance but in only one tumor was there a neoplastic component of epithelial form. Eight tumors (20%) showed evidence of malignant behavior. All of these were large and cellular at the time of initial surgery and four had mitotic counts of 10 or more/10 H.P.F. in areas. The evidence suggests that the great majority of localized pleural tumors arise from submesothelial mesenchymal elements and it is believed that the term mesothelioma should not be used in reference to these growths.     

A left pleural effusion with a calcified tumoral mass and left hemithoracic uptake on bone scan

Diffuse malignant pleural mesothelioma is a rare primary tumor of the pleura with three principal histological types, epithelial; mesenchymal and mixed epithelial and mesenchymal. We report here a case of a mesenchymal mesothelioma with foci of osteosarcomatous degeneration revealed by dense calcifications associated with the pleural effusion on the computed tomography (CT) of the thorax. The bone scan revealed extraosseous uptake corresponding to the left pleura.     

Streptozotocin-induced renal tumours in rats.

Forty-six separate renal tumours developed in 36/80 Wistar male rats given a single i.v. dose of streptozotocin (25 mg/kg body wt) to induce diabetes mellitus. Fourteen of the tumours were epithelial in type, 8 were wholly mesenchymal and 24 were largely mesenchymal but also contained epithelial elements. The purely epithelial tumours correspond to the renal adenomas and adenocarcinomas seen in man. The mesenchymal tumours were composed either of undifferentiated spindle cells or of a mixutre of poorly differentiated mesenchyme and epithelial glands. Microscopically, the mixed tumours resembled the nephroblastomas seen in man; both elements appeared to be malignant, but in the absence of metastases this remains unproven. The management of the diabetic state did not influence the incidence of tumours, but insulin appeared to enhance tumour growth.     

A case of mixed mesodermal tumor of the uterus with alpha-fetoprotein production

A case of mixed mesodermal tumor of the uterus with alpha-fetoprotein (AFP) production in a postmenopausal woman is reported, with special reference to its histogenesis. Judging from the serum AFP levels, the AFP content of the tumor and immunohistochemical localization of AFP in the tumor, AFP was produced by the tumor. The observation that in this patient AFP existed exclusively in carcinoma cells strongly supports the hypothesis that malignant transformation of Müllerian epithelial and stromal cells in mixed mesodermal tumors of the uterus occurs independently after the primitive mesenchymal cells have differentiated towards epithelial and stromal components.     

Adenocarcinoma of the rete testis with a spindle cell component. A possible metaplastic carcinoma

A case of adenocarcinoma of the rete testis was encountered in a 36-year-old white man. The tumor fulfilled established criteria for determining origin in the rete and showed an unusual biphasic morphology with papillary adenocarcinoma mixed with a prominent component of cytologically malignant spindle cells. Immunohistochemical study demonstrated a positive reaction in the epithelium for cytokeratin and epithelial membrane antigen, and the cytoplasm of a few of the spindle cells also reacted with these antibodies. Electron microscopic study confirmed the biphasic pattern, showing epithelial gland formation and mesenchymal cells. The results indicate that this tumor is a metaplastic carcinoma of the rete testis. Recognition of this pattern of rete carcinoma may further enhance our knowledge of primary tumors at this unusual site.     

An ultrastructural study of mixed hepatoblastoma with osteoid elements.

A case of mixed hepatoblastoma with osteoid elements was studied by light and electron microscopy. The ultrastructure of the epithelial elements showed a lack of differentiation and simple cytoplasmic organelles. However, an occasional cytoplasmic crystalloid structure were seen. The ultrastructure of the osteoid foci showed fibroblast-like cells capable of collagen formation, clearly distinguishable from the epithelial elements. These cells had neoplastic characteristics of nuclear pleomorphism and high nucleo-cytoplasmic ratio. These findings support the belief that hepatoblastoma arises from a multipotential blastema capable of both epithelial and mesenchymal differentiation, with the osteoid elements being an intrinsic neoplastic component of the tumor.     

A Correlative Study of N-Cadherin Expression with Different Grades of Oral Squamous Cell Carcinoma Projecting as a Marker of Epithelial to Mesenchymal Transition in Tumor Progression

Background: Epithelial cells typically express E-cadherin where as N-cadherin expressed by mesenchymal cells.The epithelial to mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell-celladhesion, and gain migratory and invasive properties to become mesenchymal cells. EMT is typical for carcinoma cellsduring tumor progression and correlate with the local invasiveness and metastatic potential of the tumor. Oral squamouscell carcinoma is a malignant neoplasm arising from the mucosal epithelium of the oral cavity. It can be classifiedas well; moderate and poor depends on a tumor cells resemblance to its tissue of origin. Materials and Methods: Atotal of 130 cases of histopathologically diagnosed as OSCC were selected for the study, out of which 66,38 and 26were well, moderate and poorly differentiated respectively. One section was stained with Haematoxylin and Eosinand the other section for N-cadherin immunohistochemical study. Then the N-cadherin expression was correlatedhistopathologically with different grades of OSCC. Statistical analysis was carried out mainly by Chi-Square analysis.Results: Among the 66 cases of WDSCC mean value of N-cadherin expression was 1.79, 38 cases of MDSCC meanvalue of N-cadherin expression was 4.16 and among the 26 cases of PDSCC the mean value was 6.38.That means thevalue of N- cadherin expression was progressively increasing with decreased differentiation of the tumor cells. Thestatistical analysis also shown it was highly significant (P<0.001). Conclusion: A correlative study of N-cadherinexpression with different grades of OSCC will be useful to predict the state of tumor progression and also it may giveaccuracy for histopathogical grading of the tumor.     

Immunocytochemical study of an endometrial diffuse clear cell stromal sarcoma and other endometrial stromal sarcomas

Intermediate filament composition was studied in the following endometrial stromal tumors: low-grade stromal sarcoma (endolymphatic stromal myosis), high-grade stromal sarcoma with an associated adenocarcinoma (collision tumor), diffuse clear cell stromal sarcoma and a mesodermal mixed tumor (carcinosarcoma). The tumor cells of the stromal tumors as well as the mesenchymal elements of the mixed mesodermal tumor were decorated exclusively with antibodies to vimentin. Desmin was not demonstrated in these tumor cells. A biochemical study of the cytoskeletal filaments present in the low-grade stromal sarcoma revealed, in addition to vimentin, beta and gamma actin as seen in normal endometrial stroma. Cytokeratins were only identified in epithelial components which were present in some of these tumors. Intermediate filament typing in these endometrial neoplasms contributes to the elucidation of histogenetic problems, may delineate mesenchymal from epithelial elements, may separate muscle from stromal lesions and in one instance helped to define a hitherto unreported diffuse clear cell stromal sarcoma.     

Carcinosarcoma of the gallbladder. A case report with immunohistochemical and ultrastructural studies

The authors present the histologic features, immunohistochemical findings, and ultrastructure of a carcinosarcoma of the gallbladder containing rhabdomyosarcoma as a mesenchymal element. A pedunculated polypoid tumor protruded into the lumen from the fundus of the gallbladder. The neoplasm contained two divergent components. One was malignant mesenchymal tissue with rhabdomyoblastic differentiation; the other was ordinary adenocarcinoma which was observed predominantly at the base of the polyp. Immunohistochemically, the cytoplasm of the rhabdomyoblasts stained with anti-myoglobin, myosin, and muscle actin antibodies. Ultrastructurally, there were a large number of malignant mesenchymal tissues in which various stages of differentiated rhabdomyoblasts were noted. Ultrastructural study was particularly valuable for the identification of sarcomatous elements.     

Sclerosing hemangioma of the lung. Immunohistochemical demonstration of mesenchymal origin using antibodies to tissue-specific intermediate filaments

A case of pulmonary sclerosing hemangioma of the lung was studied by light microscopy and indirect immunofluorescence using tissue-specific antibodies against intermediate filament subunits. All the tumor cells stained positively and exclusively with antivimentin antibodies thus indicating their mesenchymal origin. In addition, positive staining with cytokeratin antibodies was observed in cells lining cystic spaces and elongated slit-like spaces were occasionally encountered throughout the tumor, disclosing residual epithelial elements. Using brightfield microscopy, the keratin-positive areas were identified as distorted alveolar spaces lined by hyperplastic respiratory epithelium entrapped within the tumor. It is proposed that these entrapped epithelial elements may account for the conflicting results obtained by different investigators in previous attempts to determine the histogenesis of this tumor.     

c-Met信号通路在多种恶性肿瘤中的研究进展

近年来,恶性肿瘤的治疗已进入了个体化和分子靶向时代,因此,研发针对肿瘤病人个体新的治疗靶点已成为重中之重。大量临床和基础实验研究发现,由间质细胞产生的肝细胞生长因子(Hepatocyte growth factor receptor,HGF)与上皮细胞中的特异受体间质——上皮细胞转化因子(Mesenchymal-epithelial transition factor,c-Met)结合并激活该受体的酪氨酸活性,促进多种类型细胞的生长、迁移和形态学改变,继而促进肿瘤的侵袭、转移和血管生成。在甲状腺癌、乳腺癌、肺癌、头颈部鳞癌、中枢神经系统肿瘤及消化系统肿瘤的发生、发展中,HGF及其受体c-Met起着重要作用。HGF/c-Met信号通路作为多种实体瘤的新靶点,被认为是近年来最有前景的治疗靶点,已成为目前研究的热点之一。本文将主要就HGF及c-Met受体的结构、功能、激活机制及在多种恶性肿瘤中的研究进展做一综述。