[Molecular classification of urogenital cancers]. / Az urogenitális daganatok molekuláris klasszifikációja.

The molecular genetic dogma is valid that the histological variants of a given cancer represent genetic variants. Basis of this subclassification is known in clear cell renal cancer but still a mistery in prostate or bladder cancers. Meanwhile another genetic dogma developed recently that a given histological variant of a cancer can further be subdivided based on molecular characteristics. Best examples are clear cell renal cancer, adenocarcinoma of the prostate or transitional cell carcinoma of the bladder. This new knowledge helps in the differential diagnostics of cancer, and in determining prognosis, but also provides an opportunity to better tailor existing therapies even to consider novel target agents. Discovery of the molecular subtypes of cancers (such as leukemia or lung adenocarcinoma) contributed significantly to the extension of the progression-free or overall survival of cancer patients, and it is expected that it could lead to similar effects in case of urogenital cancers.

Practical issues and pitfalls in staging tumors of the genitourinary tract.

Accurate staging of tumors involving the genitourinary tract is critical to determine appropriate management options and subsequent clinical outcome for patients. The staging protocols, however, continue to evolve and are under constant revision and change. The new 2010 American Joint Committee on Cancer/Tumor Nodes and Metastasis (AJCC/TNM) staging system of the prostate, bladder, kidney, and testis is now recommended. Although the protocols are relatively straightforward, this article focuses on some practical issues and occasional pitfalls that may be encountered when staging cancers of the genitourinary tract. Specific issues that will be addressed include issues and pitfalls in radical prostatectomy specimens (substaging of pT2 tumors, extraprostatic extension, bladder neck invasion, positive surgical margins, seminal vesicle involvement, no residual tumor identified), cystectomy/cystoprostatectomy specimens (extravesicular extension and prostatic stromal invasion), nephrectomy specimens (renal sinus invasion, ipsilateral adrenal gland invasion, renal vein involvement, multifocal tumors), and orchiectomy specimens (pseudoangiolymphatic invasion of friable tumors, rete testis invasion, and spermatic cord invasion/metastasis). In addition, pitfalls in both prostate (extraprostatic extension, seminal vesicle/ejaculatory duct involvement in needle core biopsies, and quantification of tumor volume in transurethral resection specimens) and bladder (tumors with inverted growth pattern, muscularis propria invasion, extravesicular extension) biopsy interpretations that may have an impact on staging are also addressed.

Genitourinary Pathology Reporting Parameters Most Relevant to the Medical Oncologist.

Pathologic variables play an important role in prognostication in urologic malignancies. Histologic subtype, histologic grade, and anatomic extent of disease (pathologic tumor and nodal staging) influence treatment decisions in both the adjuvant and metastatic settings. This article discusses treatment paradigms for the most common urologic malignancies, followed by the evidence base to support the relationship between pathologic assessment and decision making by the medical oncologist.

Unusual Sites of High-Grade Neuroendocrine Carcinomas: A Case Series and Review of the Literature.

BACKGROUND Neuroendocrine tumors (NETs) encompass a diverse group of varying clinicopathological entities arising from cells of the endocrine and nervous systems. The presentation of these unique tumors can range from occult disease discovered incidentally to hyperactive, metastatic secretory tumors. NETs most commonly originate in the gastrointestinal and respiratory tract, although they may occur at any site in the body due to the wide distribution of neuroendocrine cells. Their classification system is complex and continues to evolve, and the current system uses histological grade in defining these subtypes. Neuroendocrine carcinomas (NECs), or high-grade, poorly-differentiated NETs, are the most aggressive subtype. Surgical resection remains the primary treatment modality and may be curative, thus early diagnosis is paramount. Management of advanced NETs remains both a diagnostic and therapeutic challenge; however, advances in our understanding of these unique neoplasms as well as an evolving classification system has led to the development of adjunctive therapeutic approaches aimed to minimize morbidity and improve patient outcomes. CASE REPORT We present 6 cases of unusual sites of high-grade neuroendocrine carcinomas involving the cervix, gallbladder, oesophagus, ovary, prostate, and urinary bladder. CONCLUSIONS Our case series highlights the heterogenous and aggressive nature of this subtype of NETs as well as their diagnostic and therapeutic difficulties. We also review the evolution of the NET classification system and its impact on the management of these malignancies.

A Genitourinary Cancer-specific Scoring System for the Prediction of Survival in Patients with Bone Metastasis: A Retrospective Analysis of Prostate Cancer, Renal Cell Carcinoma, and Urothelial Carcinoma.

AIM: The aim of this study was to develop a risk scoring system specific to patients with bone metastasis of genitourinary cancer. MATERIALS AND METHODS: This study included 180 patients with bone metastasis of three major types of genitourinary cancer: prostate cancer (n=111), renal cell carcinoma (n=43,), and urothelial carcinoma (n=26). Clinical factors at diagnosis of bone metastasis were evaluated to identify independent prognostic factors. RESULTS: Multivariate analysis showed that type of primary cancer, poor performance status, the presence of visceral metastases, high Glasgow prognostic score and elevated neutrophil-to-lymphocyte ratio were independently predictive of poor prognosis. Patients were able to be classified by the prognostic risk score into four prognostic groups with low, intermediate, high, and very high risk. CONCLUSION: This risk scoring system could be useful for predicting survival of patients with bone metastasis of genitourinary cancer and in making decisions on appropriate treatments for them.

Neuroendocrine tumours in rare sites: differences in nomenclature and diagnostics-a rare and ubiquitous histotype.

The diagnosis of neuroendocrine tumours in typical sites, as gastrointestinal tract and lung, is based upon well-coded criteria that have become familiar to most of the pathologists. Much more difficult is the recognition and allocation of proper nomenclature to be referred to the same histotype in locations where these tumours have a lower incidence. The aim of our review was to provide a quick handbook of the main diagnostic pitfalls known in literature that can interpose in the histopathological examination of neuroendocrine tumours in rare sites (urinary system and male genital organs, female genital organs, head and neck and breast).

[Computer tomography for TNM based radiation planning of urological tumours (author's transl]. / Unterstützung einer am TNM-System orientierten Bestrahlungsplanung urologischer Tumoren durch die Computertomographie.

From the extensive statistics concerning treatment results of urological tumours which are available from central tumour registers, a first draft of a treatment plan has been worked out, which is based on tumour spread. Since the extent of tumour invasion is documented by the TNM system of the UICC, one is justified in speaking of TNM orientated treatment planning. For planning it is necessary to consider not only tumour type and depth of infiltration of local tissues, but also the lymph node anatomy, whether the nodes are involved or not. Computer tomography assist significantly in the performance of such TNM orientated treatment planning, particularly in determining the extent of the volume to be irradiated, It must be stressed that computer tomography does not replace the use of simulators, but that it is a valuable addition. In our view, computer tomography has also an undoubted value in treatment planning of urological tumours where palliation only is the aim. It provides the possibility of checking the effect of the chosen treatment by a non-invasive diagnostic method.

[TNM classification].

Stage classification of cancer is a method for objectively describing the status of a tumor. For more than 30 years, the TNM classification system was applied on various kind of malignant neoplasms, whose basic principles were: 1) applicability to all anatomic sites; 2) independence from treatment, and 3) susceptibility to further modification on the basis of information supplied by surgery and histopathological description. Thus far, TNM classification system has made a great contribution to 1) aid the clinician in the planning of treatment; 2) give some indication of prognosis; 3) assist in evaluation of the results of treatment; 4) facilitate the exchange of information between treatment centers; 5) contribute to the continuing investigation of human cancer. However, the publication of the fourth edition of the TNM classification has caused great consternation to urologists because of lack of logic for its complete revision. In this review analyses were done on the changes in the TNM classification of the genitourinary tumors described in the 3rd, 4th and 4th revision. Discussion was also made in relation to the TNM systems and classification systems in the general rules for clinical and pathological studies on urological malignancy of Japanese Urological Association.

Dense pattern of embryonal rhabdomyosarcoma, a lesion easily confused with alveolar rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.

OBJECTIVES: To examine whether the frequency of fusion-negative alveolar rhabdomyosarcoma (ARMSn) increased coincident with changes in the definition of alveolar histology. METHODS: We re-reviewed alveolar rhabdomyosarcoma (ARMS) in the Children's Oncology Group study D9803, comparing histopathology with fusion status. RESULTS: Our review of 255 original ARMS cases (compared with a control group of 38 embryonal rhabdomyosarcomas [ERMS] cases) revealed that many had an ARMS-like densely cellular pattern with cytologic features and myogenin expression more typical of ERMS. Following re-review, 84 (33%) cases of original ARMS were rediagnosed as ERMS. All reclassified ERMS, including dense ERMS, were fusion negative, whereas 82% of confirmed ARMS cases were fusion positive. Total ARMS diagnoses returned to historic rates of 25% to 30% of all rhabdomyosarcomas, and ARMSn decreased from 37% to 18% of ARMS cases. The outcome of reclassified ERMS was similar to confirmed ERMS. CONCLUSIONS: To address the role of fusion status in risk stratification, pathologists should include both a histologic diagnosis and an evaluation of fusion status for all new ARMS diagnoses.

[Towards the individualisation of prescriptions in oncology: urogenital cancers]. / Cancers génito-urinaires.

The daily management of urogenital cancers is currently based on prognostic classifications derived from the identification of independent clinical or biological indicators of overall survival. These classifications are used for patient stratification in clinical trials and definition of appropriate strategies according to prognostic groups. Their knowledge is therefore essential for optimizing treatment decisions. Metastatic germ cell tumours and renal cell cancers as well as localised prostate cancers are classical models for the development of such classifications. The emergence of targeted therapies and the identification of predictive parameters for treatment efficacy should represent a further step towards the emergence of individualized treatments in the near future.

Studies on tumourous and other urogenital patients with respect to antigens of oncogenic adenovirus.

The possible connection of viruses with tumours was investigated by serologic examinations. Concerning the presence of antibodies against adenoviruses, especially those against the early non-virion antigens of oncogenic adenovirus type 12, approximately 4000 tests were made with sera of 446 urogenital patients with and without tumours and 70 ones with internal diseases. It was found by complement fixation tests that antibodies against nonvirion antigens of adenoviruses were present in 53% of urogenital patients suffering from malignant tumours and prostatic hypertrophy, in 18% of non-tumourous urological patients and in 4% of patients with internal diseases, respectively. The results suggest that adenoviruses may play a role in tumourous diseases of the urogenital organs.

TNM classification of genitourinary tumours 1987--position of the EORTC Genitourinary Group.

This report analyses the changes in the classification of the genitourinary tumours introduced by the 1987 edition of the TNM system. Criticism and suggestions for improvement are given. These are based on the extensive experience of the EORTC GU Group with clinical trial work particularly the identification of prognostic factors, on their success in reaching international consensus on tumour classification, and on information from the literature. Many of the changes introduced in the 1987 system are not considered to be strictly necessary. These include the introduction of the new additional descriptors, including "C" and "R", the changes in the T classification of prostatic and renal cancer, and the introduction of uniform N categories for all tumours and other features. We regret the omission of minimal requirements, the omission of the V classification for macroscopic or microscopic vascular invasion, the changes in the T categories of carcinoma of the bladder and the introduction of stage groupings for all urological tumours. Some of these changes are considered unacceptable. The attitude of the EORTC GU Group toward the use of the new TNM classification is indicated in detail.

Pediatric genitourinary tumors.

Although genitourinary tumors make up only 10% of childhood cancers, with Wilms' tumor accounting for most, the study of these tumors has yielded a model of cancer development. Tremendous interinstitutional and international cooperation has improved the survival and lowered the morbidity of treatment. Advances in molecular biology and improvement in experimental techniques make this a tremendously exciting field, with discoveries being made almost routinely. Most importantly, however, the study of this group of tumors and the ensuing application of multi-modality therapy has saved the lives of thousands of children.

Rare and unusual tumors of the genitourinary tract.

The entity of small cell undifferentiated carcinoma of the urinary tract is clearly recognized, though treatment still poses considerable difficulties. Small cell undifferentiated carcinoma may lead to systemic symptoms by hormone production, even in patients with localized tumors. The survival rates of adults with Wilms' tumor approach only 50% of those seen in children. Cisplatin may be effective in relapsing patients. Cancer of the female urethra should be treated by combined surgery and radiotherapy. One should differentiate between urachal and nonurachal adenocarcinoma. DNA ploidy seems to be an important prognostic parameter in adenocarcinoma of the bladder. After orchiectomy, adjuvant chemotherapy is recommended even in testis-confined malignant lymphoma. Organ-preserving surgery and radiotherapy should be used in malignant lymphoma of the bladder. Patients with uncommon urologic tumors should be treated at larger cancer centers. Alternatively, the clinician should at least enter relevant information on patients seen with these malignancies into collective databases. This review summarizes the clinical aspects of rare and unusual tumors of the genitourinary tract in adults.