High-grade prostatic sarcoma seen in a catheterized urine specimen: case report and differential diagnosis.

Urine cytology has been effectively used in the diagnosis and management of epithelial bladder tumors, particularly high-grade urothelial carcinoma. Indeed it is the gold standard for bladder cancer screening. Although urothelial carcinoma is the most frequently identified bladder tumor by urine cytology, metastatic carcinomas from the kidney, colon, and a variety of other regional organs have been detected. Stromal lesions such as inflammatory myofibroblastic tumor, gastrointestinal stromal tumor, and leiomyosarcoma are other much rarer entities occurring within the bladder. Few to no case reports exist documenting their identification within urine cytology specimens. Herein we report the detection of a high-grade prostatic sarcoma within a catheterized urine specimen of a young male having a diffusely enlarged prostate. The specimen consisted of numerous fragments of relatively uniform spindle cells having ovoid nuclei with rounded ends and finely dispersed chromatin. Cytoplasmic borders were indistinct. No mitoses or significant atypia was present. The background consisted of numerous red blood cells, cellular debris, and a few clusters of unremarkable urothelial cells. Followup surgical biopsy of the patient's prostate revealed a high-grade spindle-cell sarcoma. Further immunohistochemical and molecular delineation of the tumor was not informative for a more definitive diagnosis. Although rare, sarcomas and other mesenchymal tumors involving the bladder are unique entities with a broad differential diagnosis.

Sarcomatoid collecting duct carcinoma of kidney diagnosed with urine and renal pelvic lavage cytology.

A case of sarcomatoid collecting duct carcinoma (CDC) of kidney is presented, in which the diagnosis was made cytologically with voided urine and renal pelvis lavage. Cytology of hemorrhagic voided urine revealed highly atypical adenocarcinoma cells with reminiscent ductal structure, which suggested CDC as the most likely diagnosis. Computed tomography and magnetic resonance imaging demonstrated a left renal tumor, and selective lavage of left renal pelvis yielded spindle-shaped, highly atypical cells that indicated sarcomatoid carcinoma. The diagnosis of renal cancer with urine cytology is challenging because of small number of tumor cells in the urine, which are often associated with degeneration. As the urinary cytologic findings of sarcomatoid CDC have not been reported, the characteristic cytologic findings of sarcomatoid CDC are described in detail, and the differential diagnoses with diagnostic pitfalls were discussed.

Angiostatin fragments in urine from patients with malignant disease.

Angiostatin, a family of fragments originating from the NH2-terminal portion of plasminogen, has been described as a potent inhibitor of angiogenesis. In order to examine to what extent angiostatin can be detected in cancer patients, urine was collected from 117 patients with different types of malignancies and subjected to Western blot analysis, utilizing antibodies raised against "kringles" 1-3 in plasminogen. A heterogeneous mixture of fragments was observed, with patterns that also varied between patients. Angiostatin fragments were quantified by densitometric scanning. The concentrations were 27 +/- 75 (SD) micrograms L-1 (range, 1-565 micrograms L-1) in urine from cancer patients, as compared to 3 +/- 2 (SD) micrograms L-1 (range, 1-10 micrograms L-1) in urine from healthy individuals. Thirty-three patients (28%) had elevated levels using a cut off level at 15 micrograms L-1 (clearly above the highest level obtained among control subjects). NH2-terminal amino acid sequence analysis of purified angiostatin fragments from one patient showed a heterogeneous pattern, but were consistent with the region between the preactivation peptide in plasminogen and "kringle" 1, as expected. Several of the patients with urinary angiostatin showed signs of poor kidney function. We conclude that angiostatin can be detected in urine from cancer patients, but at present, the clinical significance of this finding is unclear.

Hypouricemia and cancer. A study of the mechanisms of renal urate wasting in two cases.

Two cases of hypouricemia in association with malignant diseases are presented. One patient had metastatic breast cancer and the other an undifferentiated retroperitoneal sarcoma of the childhood. Uric acid renal handling was studied with the pyrazinamide and benzbromarone tests. Both patients had reduced postsecretory reabsorption of uric acid. The increase of serum uric acid levels in both patients, after a partial response to chemotherapy, indicates the possible paraneoplastic origin of hypouricemia. Our results are discussed and compared with other reports in the literature.

Determination of the urinary excretion of ifosfamide and its phosphorated metabolites by phosphorus-31 nuclear magnetic resonance spectroscopy.

Phosphorus-31 nuclear magnetic resonance spectroscopy was used to analyze urine samples obtained from patients treated with ifosfamide (IF). This technique allows the individual assay of all phosphorated metabolites of IF in a single analysis without the need for prior extraction. In addition to the classic IF metabolites 2-dechloroethylifosfamide (2DEC1IF), 3-dechloroethylifosfamide (3DEC1IF), carboxyifosfamide (CARBOXYIF), and isophosphoramide mustard (IPM), several signals corresponding to unknown phosphorated compounds were observed. Four of them were identified: one is alcoifosfamide (ALCOIF), two come from the degradation of 2,3-didechloroethylifosfamide (2,3-DEC1IF), and one results from the decomposition of 2DEC1IF. The total cumulative drug excretion as measured over 24 h in nine patients was 51% of the injected IF dose; 18% of the dose was recovered as unchanged IF. The major urinary metabolites were the dechloroethylated compounds, with 3DEC1IF excretion (11% of the injected dose) always being superior to 2DEC1IF elimination (4% of the injected dose). Degradation compounds of 2DEC1IF and 2,3DEC1IF represented 0.4% of the injected dose. The metabolites of the dechloroethylation pathway always predominated over those of the activation pathway (CARBOXYIF, ALCOIF, and IPM, representing 3%, 0.8%, and 0.2% of the injected dose, respectively). In all, 14% of the injected dose was excreted as unknown phosphorated compounds. The interpatient variation in levels of IF metabolites was obvious and involved all of the metabolites. Renal excretion was not complete at 24 h, since 11% of the injected dose was recovered in the 24- to 48-h urine samples.

[Increase of excretion of urinary catecholamines and its catabolites in a case of pulmonary sarcomatous tumor]. / Elévation de l'excrétion des catécholamines urinaires et de leurs catabolites dans le cas d'une tumeur sarcomateuse pulmonaire.

A five-year-old child presented with a large undifferentiated sarcoma in the right lung. Urinary catecholamines were assayed as tumor markers. A short-lived but significant rise in urinary norepinephrine and dopamine followed by rises in urinary levels of corresponding breakdown products were evidenced.

Identification of an immunoreactive glycoprotein in the urine of sarcoma patients.

Tumor-associated antigens (TAA) can be detected in the urine of sarcoma patients by a variety of assays. This study was designed to correlate antigen activity in three assays: complement fixation assay (CFA), enzyme-linked immunosorbent assay (ELISA), and Western blot (WB). This study identifies the antibody class responsible for TAA identification in these assays and characterizes the nature of the antigen. One hundred eighty-nine urine samples from eight sarcoma patients with known levels of TAA in CFA were tested in ELISA and WB. Allogeneic anti-TAA containing sera (1 degree antibody) from a sarcoma patient was reacted with urine samples followed by detection with alkaline phosphatase-linked goat anti-human IgG and IgM (2 degree antibody in both assays). Reactivity in CFA correlated to IgM reactivity in ELISA and WB (chi 2 test, P less than 0.001). No correlation was found to IgG reactivity in either assay. Reactivity in WB vs ELISA was also highly correlated for IgM (P less than 0.001). TAA was visualized in WB as a distinct pattern of repeating bands, with most bands being detected in the range 30,000-60,000 Da. The separation between bands approximated 2500-3000 Da, suggesting a molecule composed of repeating subunits. This study suggests that the antigen is glycoprotein in nature, and that the detecting antibody is of the IgM class.

Indomethacin responsive hypercalcaemia associated with a renal sarcoma.

An infant presented with a non-metastatic renal spindle cell sarcoma and hypercalcaemia, which resolved after treatment with indomethacin. There was in vivo and in vitro evidence that hypercalcaemia was mediated by circulatory prostaglandins.

Urinary neopterin excretion in patients with uterine sarcomas.

Neopterin, a pyrazinopyrimidine compound, is a marker of activation of cell-mediated immunity. Urinary neopterin concentrations were measured in a total of 44 patients with uterine sarcomas. Pretherapeutic neopterin excretions were elevated in 78% (14/18). The mean neopterin concentration of patients with sarcomas was significantly higher (P less than 0.0001) than that obtained in women with benign myomas and healthy controls. Furthermore, a significant correlation of normal or raised neopterin concentrations with the clinical course of disease was found. These data suggest that urinary neopterin measurement might be a useful immunologic marker for women with uterine sarcomas.

A prospective postoperative evaluation of urinary tumor-associated antigens in sarcoma patients. Correlation with disease recurrence.

Tumor-associated antigens (TAA) excreted into the urine of sarcoma patients can be detected by the complement-fixation assay. The authors prospectively measured TAA levels in the urine of 50 sarcoma patients postoperatively to determine whether reappearance of antigen in the urine would be predictive of disease recurrence. Twenty-five patients developed recurrence of their disease in the postoperative period, and 24 (96%) had reappearance of antigen in the urine 10.1 +/- 9.2 months prior to clinical evidence of recurrence. Of the 25 patients who remained disease free (mean follow-up, 48 months), 23 of 25 (92%) were urinary-antigen negative at last follow-up, although 8 patients had transient elevations of urinary TAA early in the postoperative period. Results indicate that postoperative measurement of urinary TAA in sarcoma patients permits selection of a subset of individuals at high risk for the development of recurrence. This knowledge can be of assistance in the postoperative management of these patients.

Transforming growth factors in the urine of normal, pregnant, and tumor-bearing humans.

Transforming growth factor (TGF) activities could be detected in the urine of normal, pregnant, and tumor-bearing humans. These acid- and heat-stable polypeptides competed for binding to epidermal growth factor (EGF) membrane receptors and promoted the anchorage-independent growth of nontransformed rodent cells. They differed from human EGF in their apparent molecular weights and soft-agar growth-stimulating activity. The urine from pregnant females contained TGF activities with apparent molecular weight(s) (relative) (Mr) of 10,000 ad 17,000--20,000. In the case of a lung cancer patient, an additional major activity of approximately 30,000--35,000 Mr was found. All urine specimens examined also contained a "common" 8,000-Mr soft-agar growth-stimulating activity, which competed for binding to EGF membrane receptors and which was chromatographically separable from EGF (urogastrone). Thus urine may provide a convenient and readily available source for the biochemical characterization of these TGF-like activities, some of which may be clinically useful biologic markers for certain types of cancer.

Assessment of in vivo effectiveness of tumoricidal chemotherapy and radiation therapy by serial analysis of tumor-associated urinary antigen titers in patients with sarcoma.

Serial measurements of tumor-associated antigens in the urine of patients with sarcoma who received preoperative intra-arterial doxorubicin and radiation therapy were assayed by microcomplement fixation. Changes in urinary antigen titer as a result of therapy were compared to pretreatment samples and were correlated with clinicopathologic evidence of in situ tumor cell destruction. Of the 53 patients with sarcoma studied, 44 had clinicopathologic evidence of tumor destruction induced by the preoperative therapy, and all 44 had a fourfold or greater rise in the level of urinary antigens during the treatment period. The other nine patients had no evidence of tumor destruction and antigen titers remained unchanged. Results suggested that tumoricidal therapy released tumor-associated antigens which could be detected in urine by microcomplement fixation. This phenomenon may be useful for measuring the in vivo effectiveness of tumoricidal therapy on nonaccessible tumors.

Development of an enzyme immunoassay to detect and quantitate tumor-associated antigens in the urine of sarcoma patients.

This study describes the development of an enzyme immunoassay (EIA) to quantitate antigen in the urine of sarcoma patients and compares its results with those of the authors' previously reported complement fixation assay. Three populations were studied for the presence of urinary antigen by EIA: (1) sarcoma patients who developed metastatic disease after resection of their primary tumor; (2) sarcoma patients who remain clinically disease-free two years after resection of their primary tumor; and (3) normal volunteers with no history of malignant disease. EAch group consisted of nine individuals. None of the urines from normal volunteers and none from sarcoma patients who remained free of disease for two years had elevated antigen titers detectable by EIA. However, all nine patients who developed pulmonary metastatic disease ahd significantly elevated levels of antigen in their urine prior to clinical evidence of disease recurrence. The day-to-day fluctuations in antigen titer detectable by EIA tended to parallel the levels detected by the complement fixation assay. However, EIA detected a significant elevation in antigen titer one to four months earlier than the complement fixation assay in four of the patients in whom disease recurred.

Detection of cancer-associated antigen(s) in urine of sarcoma patients.

Tumor-associated antigens were demonstrated in concentrated and dialyzed urine of several sarcoma patients with large tumor burden. The antigens were detected by complement fixation using autologous and allogeneic sera from sarcoma patients. The antigenic activity in three patients who were studied sequentially disappeared after surgical ablation of tumor. In two of these three patients, the antigenic activity reappeared before tumor recurrence. The reactivity of the sarcoma sera to the urine could be abolished by absorption of the sera with human sarcoma cells but not by normal human liver cells, which indicates that the same antigen was present in the urine and on biopsy-obtained sarcoma cells. Urine from cancer patients with high tumor burden may be useful as a source of tumor-associated antigen. Further studies on the presence of these antigens in urine of sarcoma patients may lead to a method for detecting subclinical tumor recurrence.

Excretion of metabolites of biogenic amines in patients with irradiated brain tumours.

The metabolities of biogenic amines were determined in the 24-hour urine samples of patients submitted to surgical removal of a malignant brain tumour and subsequently to telecobalt therapy of the corresponding head region. A significant increase in the excretion of 5-hydroxyindoleacetic acid (5-HIAA), vanillinmandelic acid (VMA) as well as of free 3-methoxy-4-hydroxy-phenylglycol (MHPG) during the period of irradiation was found. This increase is presumably the result of radiation induced release of their parent amines from the brain; in the case of VMA the secondary response of the peripheral sympathetic system might occur.

[The importance of chorionic gonadotropin excretion in diagnosis and therapy of testicular tumours (author's transl)]. / Zum Stellenwert des Choriongonadotropinnachweises fur die Diagnostik und Therapie der Hodentumoren

Systematic investigations of the chorionic gonadotropin excretion were performed in 79 patients with testicular tumours. The influence of the hormonal activity in diagnosis and prognosis of metastatic testicular tumours was investigated. It was discovered, that the part of hormonal active testicular tumours is relatively small and that the evidence of the chorionic gonadotropin excretion is only possible in a few cases before the clinical and radiological evidence of metastases. The hormonal activity of testicular tumours is without influence on the survival time of tumour carriers.