The first case of primary testicular germ cell tumor containing nephroblastoma as the only one non-germ cell component

Adult extrarenal nephroblastomas (Wilms' tumor) are extremely rare tumors. They show a higher incidence of non-seminomatous elements and these so-called 'teratoid' Wilms' tumors are suggested to be of germ cell origin. To date, however, the number of reported cases with gonadal teratoma containing nephroblastoma is very low, and due to this reason, there are no standardized criteria for the categorization and treatment of these lesions. To our knowledge, the first case of nephroblastoma arising in a non-atrophic testis has been reported and it is associated with a teratoma as morphologically identifiable germ cell tumor and rhabdomyosarcoma as a second non-germ cell element. We report the second case of an adult nephroblastoma that arose within the primary testicular teratoma in a non-atrophic testis. Teratoma and nephroblastoma within the same testis may have an important point to clarify the developmental mechanism in nephroblastomatous differentiation of germ cell tumors.     

Nephroblastoma with neuroendocrine differentiation

A nephroblastoma (Wilms' tumor) with morphological, histochemical, immunohistochemical and ultrastructural evidence of neuroendocrine differentiation is described. Whereas areas of neural differentiation and occasional argyrophilic cells in cases of Wilms' tumor have been previously reported, the unique characteristic in this case was the extent of the neuroendocrine differentiation, as shown by a strong Grimelius stain of over 90% of the blastematous cells. Immunoperoxidase studies employing antibodies to neuron-specific enolase and ultrastructural data were also in favor of the neuroendocrine differentiation and suggested the existence, in addition to the already reported variant of Wilms' tumor with neural differentiation, of a neuroendocrine variant which may be part of the histologic spectrum of this neoplasm.     

Differentiation dependent expression of P-glycoprotein in the normal and neoplastic human kidney.

Adult renal cell carcinoma (RCC) is clinically resistant to chemotherapy. However, in nephroblastoma (NBL) chemotherapy has increased survival dramatically. We studied the P-glycoprotein (P-gp) expression of 18 RCC and 9 NBL as well as 1 benign renal adenoma and fetal renal tissue using three different monoclonal antibodies (MRK-16, C-219, JSB-1). P-gp was found positive with all three antibodies in 12/18 RCC, while only 2 tumors were completely negative. Staining varied with respect to intensity and number of positive cells [5%-90%]. Intense staining was seen at the apical side of malignant tubules in well differentiated parts of RCC and in tubular structures of the benign renal adenoma. Poorly differentiated parts of the tumors showed less staining. In NBL blastemal parts were negative. In 4/8 specimens showing focal epithelial differentiation, however, the luminal side of more differentiated tubular structures did stain, strongly resembling P-gp staining in the developing fetal human kidney. These results indicate that P-gp expression in normal (fetal) human kidney as well as in benign and malignant tumors derived from this organ depends on the degree of differentiation of tubules, which may have implications for chemotherapy sensitivity in both malignant tumors.     

ULTRASTRUCTURAL CHARACTERISTICS OF NEPHROBLASTOMAS AND THEIR RELATION TO DNA PLOID

Fifty-one cases of nephroblastoma were pathologically studied by light and electron microscopy as well as microspectrophotometry. Under light and electron microscope, the tumor appeared to be carcinosarcoma structurally, consisting of epithelial, sarcomatous and undlfferentiated tumor cells. Their ultrastructural feature was similar to that of renal tubular epithelial cells and tibroblast. It could differentially be diagnosed from renal metoblastic tumors by electron microscopy when the tumor was mainly composed of sarcomatous cells. Microspectrophotometer measurement showed an Increased mean nuclear DNA content (DI>1. 04), belonging to aneuplold tumor, which together with polyploid cells, serving as one of the Important characteristics of malignant tumors. In addition, the poorer the tumor differentiation the higher was the DNA content of the tumor cells, suggesting that the measurement of nuclear DNA of tumor cells might also serve as one of signs to acertain the degree of differentiation and malignan     

Flow cytometric analysis of nephroblastomas and related neoplasms

A total of 59 cases of nephroblastoma and related neoplasms were studied by flow cytometry of paraffin-embedded tissue. According to clinical prognosis, cases were subdivided into three groups: Group 1 (low risk) consisted of congenital mesoblastic nephroma (n = 13) and cystic, partially differentiated nephroblastoma (n = 2). Group 2 (intermediate risk) comprised the various subtypes of "typical" nephroblastoma (n = 24) including cases of fetal rhabdomyomatous nephroblastoma (n = 4). In group 3 (high risk) there were cases of anaplastic nephroblastoma (n = 3), clear cell sarcoma of the kidney or "bone metastasizing renal tumor of childhood" (n = 7), and malignant rhabdoid tumor of the kidney (n = 6). The three clinically different groups of tumors also varied in the proportion of cases with aneuploid tumor DNA stemlines, in S-phase fractions, and in proliferation indices (PI = S + G2 + M). Group 1 was generally characterized by a small number of cases with aneuploid tumor DNA stemlines and low values for S-phase fractions and PI, whereas Group 3 showed the largest number of cases with aneuploid tumor DNA stemlines and high values for S-phase fractions and PI. Group 2 was in between. It is concluded that flow cytometry on paraffin-embedded tissue from pediatric tumors may be a useful adjunct in determining prognosis, and that the subdivision of nephroblastomas and related neoplasms into three prognostically different groups is warranted.     

Differential renal tumor response to N-ethylnitrosourea and dimethylnitrosamine in the Nb rat: basis for a new rodent model of nephroblastoma

Previous studies have indicated that the Nb rat has a higherpredisposition to the spontaneous development of nephro-blastomathan most other strains of laboratory rat. In order to determinewhether this inherent susceptibility could be exploited as amodel for Wilms' tumor, Nb rats were treated with various chemicalsin regimens known to be associated with renal tumor inductionin the young rat. Nb rats were either exposed in utero to variousdose levels of N-ethylnitrosourea (ENU) on day 18 ± 1of gestation, injected s.c. with one 25 mg/kg dose of dimethylnitrosamine(DMN) as neonates or dosed twice orally with 7,12-dimethylbenz[a]anthracene(DMBA) shortly after ovariectomy. Transplancental ENU at a doseof 60 mg/kg resulted in an average of 50% frequency of unequivocalnephroblastomas in both sexes with no renal mesenchymal tumors.In contrast, DMN administered to neonates produced a similarincidence of renal mesenchymal tumors but no nephroblastomas.DMBA in the ovariectomized female was not a successful strategyfor inducing primary renal tumors in the Nb rat (0 nephroblastomas,1 renal mesenchymal tumor in 16 effective survivors), althoughthe kidney was sometimes the site for metastatic invasion bytumors originating at other locations. The induction of nephroblastomasand renal mesenchymal tumors by ENU and DMN in parallel experimentsemphasized the many differences which establish them as distinctand unrelated tumor entities. The relatively high incidenceof nephroblastoma in the Nb rat using transplacentally administeredENU appears to represent a suitable basis for developing a rodentmodel of human nephroblastoma or Wilms' tumor.     

Expression and adhesive activity of SC1, an Ig superfamily cell adhesion molecule, in sporadic nephroblastomas of chicken

SC1, an immunoglobulin superfamily cell adhesion molecule, is transiently expressed during avian embryogenesis by a variety of cell types. This molecule has a homophilic binding activity with SC1 itself and promotes neurite projection from embryonic neurons. However, the potential role of this molecule in pathologic tissue specimens from chickens has yet to be elucidated. In this study, we examined the expression and functional role of SC1 in the sporadic nephroblastomas of chickens. Western blot analysis showed SC1 to be recognized as approximately 100 kDa and enriched in embryonic metanephros with a lower level in the adult kidney, while it was overexpressed in nephroblastomas. Immunohistochemically, SC1 was abundantly found in the tubular epithelia and blastemal cells of embryonic metanephros. In contrast, it had almost completely disappeared in the adult kidney; parts of the distal convoluted and intermediated tubules, collecting ducts, and Bowman's capsule slightly expressed SC1. In all 32 cases of nephroblastoma, SC1 was overexpressed in most characteristic components in tumors such as neoplastic epithelia with various types of differentiation, blastemal cell condensations, and glomeruloid bodies. Primary culture cells from a nephroblastoma expressed SC1 on the cell surface, whereas cells from the adult kidney showed only weak expression. A cell aggregation assay revealed that the dissociated cells from a nephroblastoma have strong aggregation activity, which was inhibited by anti-SC1 antibody. In contrast, the self-aggregation of adult chicken kidney cells was weaker than that of the tumor and not inhibited by the antibody. These findings suggest that the expression of SC1 might play a potential role in both the structural formation of nephroblastomas, based on its adhesive activity, and normal renal development.     

Primary malignant teratoma of the thyroid: case report and literature review of cervical teratomas in adults.

A case of primary malignant teratoma of the thyroid in a gravid 37-year-old female is reported and the literature on cervical teratomas in adults reviewed. The patient was treated by total thyroidectomy and left radical neck dissection followed by cervical and mediastinal radiotherapy and chemotherapy. She fied of recurrent tumor and related complications 9 months after discovery of the lesion. This is the 6th case of primary teratoma of the thyroid and the 9th case of cervical teratoma reported in a adult. These tumors are characteristically large, rapidly growing and highly malignant. The longest survival reported is 10 months. The differentiation of this lesion from carcinosarcomas of the thyroid is discussed.     

Ovarian sex cord tumor with annular tubules

A pathologic study was done on four cases of ovarian sex cord tumor with annular tubules. All four tumors occurred in young women (11-24 years of age) and were not associated with the Peutz-Jeghers syndrome. Two patients had evidence of hyperestrinism. One patient who had metastasis to the retroperitoneum, left supraclavicular lymph node, and liver confirmed the malignant potential of this tumor. Gross examination revealed tumors that were solid, yellowish, and unilateral, with varying degrees of cystic degeneration. Microscopic examination showed simple or complex annular tubules with prominent basement membranes. Many tumor cells contained lipid in the cytoplasm. Ultrastructural study showed Charcot-Bottcher filaments in all four cases, indicating Sertoli cell differentiation. True lumens and microvilli were identified in one case. The classification of the sex cord tumor with annular tubules as a Sertoli cell tumor, annular tubular type was proposed on the basis of ultrastructural findings.     

Ganglioneuroblastoma arising within a retroperitoneal mature cystic teratoma

We discuss an extremely rare case of ganglioneuroblastoma arising within a retroperitoneal mature cystic teratoma. Radiological examinations showed a cystic tumor sandwiched between the pancreas and left kidney. Surgery was scheduled because the tumor seemed to have originated from the pancreas. En-block resection of the tumor with distal pancreatectomy, splenectomy, and left adrenalectomy was performed. In terms of macroscopic appearance, the tumor mainly consisted of a unilocular cystic mass, but the presence of a smaller, solid mass was also noted within the tumor. Histopathologic examination confirmed that the cystic mass was consistent with a mature cystic teratoma of the retroperitoneum, and in addition, a ganglioneuroblastoma was evident in the solid component. Histopathologically, the ganglioneuroblastomatous area was intimately associated with dermoid tissue of the mature cystic teratoma, thus this case was diagnosed to be a mature cystic teratoma with malignant transformation. To best of our knowledge, this is the first reported case of ganglioneuroblastoma arising in a mature cystic teratoma.     

伴环状小管的卵巢性索瘤：附七例报告

Seven cases of ovarian sex cord tumor with annular tubules are reported in this paper. All lesions occurred in the young (6-25 years of age with a mean of 15 years) without Poutz-Jeghers syndrome. Four cases had estrogenic hormonal imbalance and abdominal mass. Gross examination revealed that the tumors were unilateral with smooth surface. Except one, all showed varying degrees of cystic degeneration on section. The sections appeared as roe-like granular substance in a pale yellowish brown shade in the parenchymal region. Microscopic examination showed single or complex annular tubules with prominent basement membrane-like material around the tubules. Lipid in the cytoplasm and granulosa cell tumor-like differentiation were observed in isolated area of some cases. Ultrastructurally, Charcot-Battcher filaments were found in 1 case, indicating differentiation towards Sertoli's cells. The malignant potential of this tumor had been elucidated in the literature.     

A case of sweat gland carcinoma arising in a mature cystic teratoma of the ovary

A case of sweat gland carcinoma arising in a mature cystic teratoma in a 63-year-old woman is reported. The patient was admitted with the complaint of a lower abdominal pain. Under the diagnosis of a mature cystic teratoma of the right ovary, the tumor was removed. Histologically, adenocarcinoma was found in the wall of the mature cystic teratoma. A part of the tumor showed a differentiation of the secretory portion and duct of the sweat gland. Histochemically, sialic acid containing mucoprotein was defected. Electron microscopically, the tumor cells were found to have secretory granules and intracytoplasmic canaliculi. Therefore, the tumor was diagnosed as a sweat gland carcinoma arising from a mature cystic teratoma.     

Morphological and immunohistochemical studies of the estrogen-induced Syrian hamster renal tumor: probable cell of origin

Chronic natural or synthetic estrogen treatment of Syrian golden hamsters leads to the development of malignant renal neoplasms. In the present study, morphological and immunohistochemical studies were performed to further characterize the estrogen-induced hamster renal tumors. The neoplasms were composed of two distinct cell populations: a large-cell component that appeared highly epithelial, and a poorly differentiated small-cell component. Importantly, both cell types had epithelial characteristics, since they contained desmosomes at their cell surfaces. However, the large-cell component possessed additional epithelial features such as microvilli, intracytoplasmic lumens, and cilia. Comparative studies of renal tumors and developing renal tissue from fetal and newborn hamsters revealed remarkable histological similarities. Morphologically, the large tumor cells resembled early metanephric tubules and the small tumor cells were very similar to the blastemal cells of the developing kidney. The earliest tumor foci were found after 4.5 months of treatment. They were consistently found in the kidney interstitium in proximity to large arteries. Immunohistochemical staining for intermediate filaments in developing fetal and newborn kidneys demonstrated cytokeratin in renal tubules, desmin in blastemal cells, and vimentin in stromal cells. Estrogen-induced renal tumor cells uniquely possessed reactivity for all three intermediate filaments, clearly demonstrating their epithelial and mesenchymal characteristics. Based on their morphological resemblance to developing embryonic kidney cells and the presence of both epithelial and mesenchymal intermediate filaments, our findings provide strong evidence that the cell of origin of this malignant tumor is a precursor cell that is committed to an epithelial differentiation pathway.     

Cystic nephroma.

The clinical and pathologic findings of four cases of cystic nephroma (so-called "renal multilocular cyst") in four infants nephrectomized with the diagnosis of Wilms' tumor are presented. Each lesion consisted of an encapsulated mass composed of cysts separated by thin septa. Histologically the cysts were lined by epithelium, and the septa contained foci of immature metanephric blastema (abundant in one case and sparse in another). rhabdomyocytes and mature tubules. Neither embryonic ducts nor cartilage were seen. One cystic lesion was adjacent to a nephroblastoma which formed a separate nodule. No recurrences of metastases developed, and the only death was due to postoperative sepsis. These lesions are considered by some authors to be dysplasia, while others interpret them as benign neoplasms. Our findings and a review of the literature probably represent the differentiated counterpart of nephroblastoma.     

Signet ring cell-type adenocarcinoma arising in a mature teratoma of the testis

A 48-year-old male who presented with an enlarged right scrotum was diagnosed with malignant transformation of testicular teratoma. Physical examination revealed a right scrotal mass of hard consistency with no inguinal lymphadenopathy. Since prepuberty, his right testis had been larger than the left one, with no pain or tenderness. Computed tomography and bone scan revealed retroperitoneal lymphadenopathy and multiple bone metastases. Right orchiectomy was performed immediately, and a pathological examination revealed a mature teratoma associated with adenocarcinoma, showing signet ring cell differentiation. Cisplatin-based combination chemotherapy was administered; however, the metastatic lesions progressed, and the patient succumbed to the disease after 15 months. Only a few cases of primary malignant transformation of teratoma in the testis have been reported, and this is the first case report of primary malignant transformation of teratoma in the testis with signet ring cell-type differentiation.     

Immunofluorescent characterization of rat kidney tumors according to the distribution of actin as revealed by specific antiactin antibody.

A series of 15 mesenchymal and 10 cortical epithelial tumors induced in the rat kidney by dimethylnitrosamine was investigated for immunofluorescent reactivity with a human antiactin antibody. Cells of epithelial tumors showed staining restricted to peripheral sites, corresponding to the brush border region. All various neoplastic cells forms comprising renal mesenchymal tumor were characterized by cytoplasmic staining in pattersn that varied with cell type. Epithelial profiles in the form of tubules and islands of epithelium showed staining patterns, or absence of them, consistent with their identity as sequestered segments of preexisting nephrons. It is suggested that the difference in actin distribution within the cytoplasm of cells of the two types of renal neoplasm, mesenchymal and epithelial, might reflect their difference in local invasive growth.     

The Ultrasonic and Angiographic Appearances of Wilms Tumours in Adults

The ultrasonic findings in three cases of Wilms Tumour (nephroblastoma) in adults are described. The appearances are not distinctive and do not help to differentiate these tumours from renal adenocarcinoma (hypernephroma). In the two cases in which angiography was performed a distinctive pattern has been seen and this may be helpful in distinguishing nephroblastoma from renal adenocarcinoma.