Bilateral testicular cancer: a preventable problem? Experience from a large cancer centre

OBJECTIVE: To report a retrospective review of patients with a testicular germ cell tumour treated in a large cancer centre who developed a second tumour, as 1.8-5% of such patients will subsequently develop a new primary tumour in the contralateral testis. PATIENTS AND METHODS: From a database of 570 men treated for testicular cancer in the West of Scotland between 1989 and 1998, all those who developed bilateral testicular tumours were identified. RESULTS: Nineteen men (3.3%) developed a second primary testicular malignancy; the mean age at diagnosis of the first tumour was 29.5 years, with the mean (range) interval to diagnosis of the second tumour of 76 (11-181) months (except for one man with synchronous tumours). The first tumour was teratoma in 11 and seminoma in seven; one patient had synchronous bilateral teratoma. The second primary was teratoma in 10 and seminoma in eight. Known risk factors for carcinoma in situ were present in nine patients, i.e. a small atrophic contralateral testis in five, a family history of testicular cancer in two, a history of infertility in two and unilateral undescended testis in one. Two patients had had contralateral testicular biopsies at the first diagnosis; both were negative for intratubular germ cell neoplasia (IGCN). Eight patients had chemotherapy to treat the first tumour and 14 for the second. All underwent bilateral orchidectomy. Overall, 18 of 19 men are alive and disease-free, with a median follow-up of 51 months. Pathology for 12 of the second testicular tumours was available for review; there was no IGCN in any of the slides from three patients, it was only present focally around the tumour in seven, and was diffuse in two patients. CONCLUSIONS: Chemotherapy for the first testicular tumour does not eliminate the risk of developing a contralateral tumour. Despite careful follow-up, in most patients the second primary tumour was not diagnosed early enough to avoid chemotherapy. The focal nature of IGCN in the second testis in most patients questions the value of biopsy of the contralateral testis. Improved methods of detecting patients at risk of second testicular tumours are needed.     

分离培养骨巨细胞瘤破骨样细胞的方法学研究

本文通过组织块贴壁法、机械分离法和酶消化法对骨巨细胞瘤的破骨样细胞进行分离、培养。通过比较,结果显示：酶消化法提纯程度最高,收获量较多;机械分离法居中,但操作简单,对原位杂交、免疫组织化学和骨吸收功能检测具有一定的应用价值;组织块培养法需要时间长,各细胞成分混杂,对研究各细胞成分之间的关系,有一定帮助     

Management of the contralateral testis in patients with testicular germ cell cancer

Patients with testicular germ cell tumours (TGCT) are at increased risk of developing a tumour in the contralateral testis. Such a tumour may be preceded by carcinoma in situ (CIS), which is more common in patients with infertility, atrophic testis or a history of cryptorchism. Of 1219 patients with TGCT seen at the Royal Marsden Hospital between 1962 and 1984 in whom the contralateral testis was managed by surveillance, 38 (3.1%) developed a second tumour and 8 died of germ cell tumours. Seventeen of 26 assessable patients (65%) exhibited at least one of the known aetiological risk factors for carcinoma in situ. Diagnosis of carcinoma in situ may lead to more appropriate management of the contralateral testis.     

Histological analysis of high-grade superficial bladder tumour

Segmental cystectomy or total cystectomy was performed in 26 patients with newly diagnosed stage T1, grade 3 transitional cell carcinoma of the bladder. Their histological specimens were assessed with regard to types of tumour cell spread, small vessel involvement and coexistent carcinoma in situ. Patients were followed for 12 to 141 months. Broad front type and tentacular type spread were seen in 57.7% and 38.5%, respectively. Small vessel involvement was seen in 38.5% of patients. Coexistent carcinoma in situ was found in as many as 65.4%. Urethral recurrence was found in 4 patients out of 26. These data suggest that the high incidence of coexistent carcinoma in situ may be the most important cause of the unsatisfactory prognosis for stage T1, grade 3 bladder cancer.     

Chromosomal high-polysomies predict tumour progression in T1 transitional cell carcinoma of the bladder

The main prognostic factor generally accepted for tumour progression in T1 transitional cell carcinoma (TCC) of the bladder is histological grade. Despite this fact it is considered inaccurate to make clinical decisions on individuals. It appears that progression from minimally invasive to deeply invasive cancer is concurrent with the acquisition of genomic alterations that increase the malignant potential of cancer cells. The aim of this study is to determine if changes in chromosomes 7, 8, 9 and 17 copy number can be used to predict recurrence and progression in patients with T1 TCC of the urinary bladder. METHODS: Thirty-one T1 TCC samples were analyzed for chromosomal alterations by fluorescence in situ hybridization using centromeric probes for chromosomes 7, 8, 9 and 17. Clinical data were collected from the patients' clinical records and correlated with chromosomal studies. RESULTS: Histological grade was confirmed as a prognostic factor of tumour progression (p=0.01). None of the cytogenetic alterations demonstrated in the studied group could be related to tumour recurrence. The high-polysomies (five or more copies) of chromosomes 8, 9 and 17 showed predictive value (p=0.05, 0.05, 0.03 respectively) for tumour progression since it was observed that patients with high-polysomy of these chromosomes showed more risk of tumour progression towards muscle-invasive disease than those without high-polysomy alteration. CONCLUSION: Our findings suggest a possible prognostic significance of highly aneuploid cells (high-polysomies of chromosomes 8, 9 and 17) in tumour progression of T1 TCC bladder tumours. FISH analysis is a reproducible technique for evaluating cytogenetic alterations and could contribute to the assessment of the individual prognosis of T1 transitional cell carcinoma of the bladder.     

Extragonadal germ cell tumour

We report a rare case of extragonadal germ cell tumour in a 55-year-old man. He presented with a painless mass in right inguinal region, a few days after hernioplasty for right direct inguinal hernia, which caused diagnostic difficulties and treatment problems.     

Antigen(s) on human transitional cell carcinoma detected by a xenogeneic antiserum

Summary In studies concerning human bladder cancer, antisera were raised in rabbits against human tumours, normal tissue, and cell lines derived from human tumours and were analysed by absorption and complement dependent microcytotoxicity tests. No significant selective cytotoxicity was discernible with any unabsorbed antisera. After absorption of A53, (an antiserum against the transitional cell carcinoma derived cell line T24) with peripheral blood cells and normal adult tissues, it was cytotoxic to two bladder cancer cell lines (T24 and J82) but not to four other cell lines. This activity was removed by absorption with each of two specimens of transitional cell carcinoma but not by normal bladder and by absorption with T24 or J82 but not with four other non-bladder cell lines. This functional specificity for transitional cell carcinomas could be due to a tumour associated antigen, a significant quantitative difference between tumour and normal cells, or an embryonic specificity reexpressed on the tumour. Further experiments are necessary to investigate these alternatives.Abbreviations used TAA tumour associated antigen(s) - NRS normal rabbit serum - MEM Eagle's minimal essential medium and additives - LuLiKi mixture of homogenates of human lung, liver and kidney - TCC transitional cell carcinoma - NBI normal bladder     

Granular cell tumour in the third ventricle

Summary A rare granular cell tumour was found in the third ventricle of a 56-year-old woman. Histological and electron-microscopic features obtained from the biopsy material were identical to those of previously recorded cases. Immunohistochemical study demonstrated vimentin but not S-100 protein in the tumour cells. The possibility should be re-considered that granular cell tumours may have more than one cell of origin.     

Small cell neuroendocrine tumour of the anterior tongue: A case report

INTRODUCTIONNeuroendocrine carcinomas (NECs) are rare in the oral cavity. There is ambiguity regarding the classification of these tumours, but their aggressive nature is recognised throughout the literature. Merkel cell carcinoma (MCC) is rare and more frequent in skin, though it has also been described intra-orally. High grade neuroendocrine tumours (HGNEC) and MCCs behave aggressively and aggressive treatment strategies have been advocated. We describe the first small cell HGNEC on the anterior tongue.PRESENTATION OF CASEWe present the first report of a pT1pN1M0 small cell HGNEC in a 75 year old man on the left lateral anterior tongue. This was widely resected with 20 mm peripheral and deep margins to achieve disease clearance. Selective neck dissection of levels 1–4 was also carried out.DISCUSSIONHistological analysis of the tumour confirmed a primary poorly differentiated neuroendocrine tumour of small cell type (small cell HGNEC). Resected node bearing tissue from levels 1–4 confirmed metastasis to a level III node with no extra capsular spread giving a pT1pN1M0 classification. Margins of 11.7 mm from the invasive tumour to mucosal margin medially and 7.0 mm for the deep margin despite surgical 20 mm margin resection. To the best of our knowledge small cell neuroendocrine carcinoma has not been described in the anterior tongue.CONCLUSIONThe aggressive nature of this tumour type mandates aggressive surgical resection with margins similar to those now recommended for skin Merkel cell carcinomas. We advocate a wide excision margin of 20 mm to give adequate clearance, with neck dissection in order to pathologically stage this cancer type.     

An unusual giant cell tumour of bone

Summary This is a report of an 18-year old girl with an unusual giant cell tumour. Although it is difficult to distinguish between a multifocal giant cell tumour of bone and a primary giant cell tumour with metastases in other bones, we believe that our case is either a multicentric or a multifocal giant cell tumour.

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Résumé Présentation d'une tumeur à cellules géantes de type inhabituel chez une jeune fille de 18 ans. Bien qu'il soit difficile de distinguer une tumeur à cellules géantes à foyers multiples d'une tumeur primitive accompagnée de métastases au niveau d'autres os, il semble bien que ce cas soit une tumeur à cellules géantes multifocale.

     

Enucleation of renal cell carcinoma with ablation of the tumour base

OBJECTIVE

To retrospectively assess the effectiveness of cancer control with enucleation of renal cell carcinoma (RCC), which is surgically expedient, allows preservation of maximal renal parenchyma, and makes intraoperative renal ischaemia unnecessary, by two surgeons routinely enucleating renal tumours and ablating the tumour bed with argon beam and the Nd‐YAG laser.

PATIENTS AND METHODS

Between 1996 and 2006 at our institution, 97 patients had RCC enucleated, with ablation of the tumour base. Patients with lesions other than RCC and those with von Hippel‐Lindau disease or Birt‐Hogg‐Dube syndrome were excluded from the study. The mean follow‐up was 24.9 months. Patients were evaluated for RCC recurrence with cross‐sectional imaging at least every 6 months for the first 2 years and then annually thereafter.

RESULTS

The mean (median, range) tumour size was 2.8 (2.5, 0.8–7.0) cm. Of the 97 patients only one had disease progression after a mean follow‐up of 24.9 months. This patient presented with a solitary grade 2 clear cell RCC and had a local recurrence 30 months after original surgery.

CONCLUSIONS

The present series and other available clinical data suggest that enucleation with cavity ablation is an oncologically sound approach that is simple, versatile and obviates the need for renal ischaemia.     

N-acetyltransferase phenotypes in bladder tumour patients with and without carcinoma in situ in selected site biopsies

The N-acetyltransferase phenotypes were revealed among 32 patients with bladder tumour and concurrent carcinoma in situ peripherally in the bladder mucosa. Fifty-nine per cent of the bladder tumour patients with concurrent carcinoma in situ were slow acetylator phenotypes in contrast to 68% of 28 bladder tumour patients with normal histological specimens peripherally in the bladder mucosa. This points to a lack of industrial arylamine bladder tumour cases in Denmark.     

Outcome and survival with nonsurgical management of renal cell carcinoma

OBJECTIVE: To document long-term survival in patients with renal cell carcinoma (RCC) in whom the primary tumour was left in situ and treatment limited to palliative and symptomatic measures. PATIENTS AND METHODS: All patients with a diagnosis of RCC from January 1994 to January 1999 and in whom the primary tumour was left in situ were identified from hospital records (nine women and 16 men, mean age 69 years). The tumour stage was T1-T4. RESULTS: The mean survival overall was 19.3 months; patients with locally advanced disease, i.e. stage >or= T3a, had a mean survival of 16.9 months. CONCLUSIONS: There is renewed interest in the management of advanced RCC, with data supporting cytoreductive nephrectomy with systemic biological therapy. These results confirm that such patients with or without metastatic disease can survive for a considerable period with no aggressive surgical or systemic measures, and such intervention may offer no significant advantage in outcome and survival over supportive treatment alone.     

A progesterone-receptor-positive huge retroperitoneal tumour mimics metastasis in a breast cancer patient: sarcomatoid renal cell carcinoma

We report a rare case of breast cancer concomitant with progesterone-receptor-positive renal cell carcinoma. A 48-year-old woman was diagnosed as having infiltrating ductal carcinoma of the breast and underwent modified radical mastectomy. A synchronous retroperitoneal tumour was detected by sonography of the abdomen in a routine cancer staging. Initially, the tumour was diagnosed as a synchronous retroperitoneal metastasis by needle biopsy; further tests revealed that it was progesterone receptor-positive. The retroperitoneal tumour showed poor response to full courses of adjuvant chemotherapy for breast cancer. Subsequently, the patient underwent a radical operation that included nephrectomy. The final pathology confirmed a sarcomatoid renal cell carcinoma. The post-operative course was uneventful. The patient had no recurrence at the 1-year follow-up. In this report, accurate diagnosis and adequate treatment were discussed. An intra-abdominal tumour with progesterone receptor- (PR) positive features is usually considered to be metastatic in breast cancer patients. For breast cancer patients with a PR-positive retroperitoneal tumour, renal cell carcinoma should be differentiated from a metastatic lesion of breast cancer, even if PR-expression is rare in renal cell carcinoma. To the best of our knowledge, this is the first case of PR-positive expression in breast cancer concomitant with renal carcinoma. In clinical settings, it is challenging for the surgeon to make an accurate diagnosis and to provide prompt treatment in such cases.     

Fine-needle aspiration biopsy of an islet cell tumour simulating pancreatic carcinoma

The importance of distinguishing between malignant islet cell tumour and pancreatic carcinoma is emphasized in this report of a 57-year-old woman who presented with an epigastric mass. Clinically and radiologically it was diagnosed as a pancreatic adenocarcinoma. A fine-needle aspiration biopsy specimen obtained under ultrasonic guidance showed tumour cells suggestive of an islet cell tumour. Immunostaining and electron microscopy were performed on the aspirate. The tumour cells stained positive with antibodies to keratin, glucagon and gastrin; ultrastructural examination revealed neurosecretory granules, confirming the diagnosis of an islet cell tumour. Angiography was performed to assess the possibility of debulking the mass. This case demonstrates the value of immunohistochemistry and electron microscopy on fine-needle aspiration biopsy specimens of the pancreas to differentiate islet cell tumours, which are potentially curable, from pancreatic adenocarcinomas, which carry a 5-year survival rate of less than 2%.     

DNA analysis in predicting survival of irradiated patients with transitional cell carcinoma of bladder.

A total of 115 patients with invasive transitional cell carcinoma of the bladder underwent radical radiotherapy between 1975 and 1986 and were followed up until the end of 1990. Apart from routine clinical observations, flow cytometric DNA measurements made on fresh tumour material were available for analysis. Actuarial cancer-free survival controlling for response to treatment was analysed with the log-rank test, bivariate and multivariate analyses using Cox's stepwise regression model on probable prognostic factors. The overall actuarial 5-year cancer-free survival rate was 30%. Survival was significantly correlated with response to treatment: 59% for patients with complete regression and 5% for those with residual tumour. Prognostic factors that significantly correlated with death from cancer were advanced stage, large size, incomplete resection, ureteric obstruction, anaemia, carcinoma in situ grade 3 and occurrence of more than one aneuploid cell population. However, only 3 of these factors were of independent power in the multivariate analysis: stage, size and carcinoma in situ. Of 21 patients with a history of primary or secondary carcinoma in situ, 19 died from cancer during follow-up: 18 of the 21 patients had tumours that were aneuploid with more than one aneuploid cell population. It is concluded that curative radiotherapy can be successful only in patients with less advanced tumours assessed according to clinical stage and size, aneuploid tumours with not more than one aneuploid cell line, no carcinoma in situ, no ureteric obstruction, and in whom a complete transurethral resection of the exophytic tumour is possible.     

Unusual intrathoracic location of a primary germ cell tumour.

The primary location of non-metastatic germ cell tumours of the chest is the anterior mediastinal compartment. Germ cell tumour arising from lung parenchyma is one of the rarest conditions in human and only a few cases of choriocarcinomas and yolk sac tumour have been reported to date. Here we report a case of intrapulmonary mixed type germ cell tumour, containing embryonal carcinoma, choriocarcinoma and yolk sac tumour elements. Diagnosis of the lesion was achieved by open thoracotomy and bulk of the tumour was resected by right upper lobectomy.     

Epstein-Barr virus infection in urothelial transitional cell carcinoma tissues

OBJECTIVE: To explore a possible correlation of Epstein-Barr virus (EBV) infection with urothelial tumours, as the mutation of oncogenes, inactivation of tumour suppressor genes and viral infections may be important in the tumorigenesis of urothelial tumours, and EBV has been implicated in the pathogenesis of a variety of lymphoproliferative disorders and several epithelial neoplasms. MATERIALS AND METHODS: In all, 104 surgical specimens of transitional cell carcinoma (TCC) were obtained from urological operating rooms, fixed in 10% buffered formalin and processed for in situ hybridization using DNA probes, to locate the signal of EBV-encoded RNAs (EBERs). Immunohistochemistry with antibodies against CD20 and EBV-encoded latent membrane protein-1 (LMP-1) was used on EBER-positive tumour specimens. RESULTS: Thirty-one tumour specimens were positive for EBER hybridization in 100 evaluable specimens. Of these positive specimens, 21 were positive in both the infiltrating B lymphocytes and TCC tumour cells, seven only in B lymphocytes and three only in TCC cells. Of 31 EBER-positive tumour tissues, 26 (84%) had LMP-1, suggesting that EBER is more sensitive than LMP-1 for detecting EBV infection. CONCLUSION: There is a strong association between EBV infection and a significant proportion of primary urothelial TCC tumour cells.     

Measurement of in vivo urological tumour cell kinetics using multiparameter flow cytometry. Preliminary study

The in vivo labelling of urological tumour cells using the S phase marker bromodeoxyuridine (BRdU) for histochemical studies is reported. The use of multiparameter flow cytometry (FCM) with BRdU labelling to study tumour proliferation offers significant advantages. It provides simultaneous measurements of the DNA ploidy (DI), the duration of the S phase (Ts), the potential doubling time (Tpot) and the total and aneuploid tumour labelling indices (LI) from a single specimen. Heterogenous tumour cell populations can be measured with high sensitivity. We report a preliminary study to evaluate the method in the measurement of the kinetics of transitional cell carcinoma of the bladder (TCCB). Nineteen patients with TCCB, 1 with leukoplakia of the bladder, 2 with renal carcinoma, 1 with prostatic carcinoma and 1 with a squamous carcinoma of the penis were studied. Of the bladder tumours, 3 were aneuploid, DI = 1.32, 1.58 and 1.89. BRdU uptake was detected in all tumours. The median LI was 1.5% (range 0.5-10.0). In 15/19 tumours the labelling profile was satisfactory for calculation of the Ts and Tpot. The median Ts was 6.2 h and the median Tpot was 17.1 days. This study demonstrates that measurement of multiple parameters of urological tumour proliferation in vivo is possible. These parameters require further assessment as indices of biological aggressiveness and clinical prognosis.