Microscopic analysis and significance of vascular architectural complexity in renal cell carcinoma.

The objective of this study was to evaluate the utility of measuring microvessel fractal dimension (MFD) as a parameter of architectural microvascular complexity in localized renal cell carcinoma (RCC). Forty-nine patients with low-stage clear cell RCC were assessed in a 9-year follow-up retrospective study. Tumor vessels were visualized with the endothelial marker CD34. Tumor microvessel density (MVD) was measured by computerized morphometry. Fractal analysis of the RCC microvascular network was performed and the MFD was computed in each case. Correlation between tumor vascular parameters, histological grade, extent of tumor necrosis and patient survival were tested by uni- and multivariate analyses. A significant correlation was found between tumor grade and decreased survival (P = 0.04). The extent of macroscopic tumor necrosis also significantly correlated with poor prognosis (P = 0.0001). Survival analysis revealed a significantly higher MVD in patients who survived longer than 5 years as compared with those who died before the end of the 5-year follow-up period (MVD = 10.8 +/- 4.7% versus 6.4 +/- 3.7%; P = 0.03). MVD was also inversely associated with the extent of tumor necrosis (P = 0.03). Microvessel fractal dimension was significantly higher in low- as compared with high-grade tumors (1.55 +/- 0.11 versus 1.45 +/- 0.15; P = 0.03). Survival analysis revealed a significantly higher MFD in those who lived >5 years as compared with those who died earlier (1.56 +/- 0.11 versus 1.46 +/- 0.15; P = 0.02). The MFD was inversely associated with the extent of tumor necrosis (P = 0.01). Multivariate analysis revealed that the MFD was the only significant factor to correlate with tumor necrosis, and that tumor necrosis was the only independent predictor of patient survival. These results indicate that the analysis of MFD as a marker of tumor microvascular complexity may provide important prognostic information as well as novel insight into the biology of tumor angiogenesis.

Development of vaginal adenosis following combined 5-fluorouracil and carbon dioxide laser treatments for diffuse vaginal condylomatosis.

BACKGROUND: The management of vaginal human papillomavirus (HPV) lesions may be difficult. We report an unusual long-term consequence of treatment. CASE: A 40-year-old woman presented with vaginal adenosis following treatment of multiple vaginal condylomata by endovaginal applications of 5% 5-fluorouracil cream and vaporization of the remaining subclinical condylomata by CO2 laser. CONCLUSION: The approach to the management of vaginal condylomatosis should take into consideration the possible later occurrence of adenosis.

Choriocarcinoma of the bladder. Report of a case of primary tumor or late metastasis of a molar pregnancy.

Choriocarcinoma of the bladder was diagnosed in a 54-year-old woman presenting with macroscopic hematuria 17 years following evacuation of a molar pregnancy. The patient was treated by cystoscopic transurethral tumor resection followed by three courses of triple-agent chemotherapy and total abdominal hysterectomy with bilateral salpingo-oophorectomy. Six months later a gradual rise in beta-human chorionic gonadotropin levels led to the diagnosis of recurrent bladder tumor at the site of the previous tumor. The patient underwent a conservative partial cystectomy, and 12 months postoperatively there was no evidence of disease. It is unclear whether the patient developed a primary urinary bladder choriocarcinoma or late metastatic disease from the previous molar pregnancy.

[Spermatocytic seminoma of the testis].

During 1968-1988, 6 patients with Stage I spermatocytic seminoma were registered at this oncology center. They represent 7% of a total of 83 patients referred for testicular seminoma (mean age 41 years, range 30-75). All 6 underwent high inguinal orchiectomy and 5 received postoperative radiotherapy. 1 refused any postoperative treatment. In a mean follow-up of 64 months (range 25-204), 4 patients were alive with no evidence of disease, 1 had died of ischemic heart disease without evidence of recurrence of the seminoma, and 1 was lost to follow-up after no evidence of disease was found 90 months after radiotherapy. In the light of our experience and reports in the literature, spermatocytic seminoma has a very good prognosis, although metastatic potential cannot be ruled out. Decision as to treatment should be based mainly on the stage of the disease.

[The vulvar clinic].

Until recently, vulvar diseases have not been given sufficient attention by gynecologists. This might be attributable to the timidity of patients with chronic vulvar pruritus, tumor or dyspareunia, which delays diagnosis and treatment. In addition, the nomenclature of vulvar disease was complicated by having been adapted from various dermatological disorders. Only following the establishment of the International Society for the Study of Vulvar Disease (ISSVD) and of specialized clinics, has awareness increased and more attention is now being paid to vulvar disorders. The findings in 242 patients seen during the first year of operation of a vulvar clinic were analyzed. The most common presenting symptom was chronic vulvar pruritus. Non-neoplastic epithelial disorder (dystrophy) was the most common histological finding in the 79 women with pruritus, while 2 were diagnosed as having vulvar intraepithelial neoplasia, and 1 had basal cell carcinoma. In contrast, vulvar vestibulitis was the main diagnosis in 34 women referred for vulvar pain (vulvodynia). Vulvodynia was also associated with other inflammatory processes and with human papilloma virus (HPV) lesions (condylomata). The primary finding in 26 women referred for evaluation of a vulvar "tumor" was epidermal cyst. In only 55 (75.5%) of the 73 referred for suspected HPV lesions was the histologic diagnosis confirmatory. In addition, a few vulvar ulcers were associated with HPV. A single treatment with carbon dioxide laser eradicated the HPV lesions in 93% of the cases. The vulvar clinic contributes to the ambulatory gynecological service by concentrating diagnosis and treatment in a single specialized unit and increases understanding of, and interest in vulvar disease.

Adenocarcinoma of the renal pelvis. Report of two cases, one with simultaneous transitional cell carcinoma of the bladder.

Mucinous adenocarcinoma of the renal pelvis is a very rare condition and represents less than 1% of renal pelvic tumors. Hydronephrosis of long duration, stones and inflammation are frequently associated with these tumors. We report 2 cases. In 1 of them, adenocarcinoma of the renal pelvis, pyelolithiasis and transitional carcinoma of the bladder were present simultaneously. The other patient had a history of abdominoperineal resection for rectal cancer 10 years prior to the renal tumor.

Synchronous and metachronous contralateral adrenal metastases from primary renal cell carcinoma.

Two rare cases of contralateral adrenal metastases are reported. One with a synchronous presentation where the renal tumor was removed together with a solitary large contralateral adrenal metastasis. The second patient underwent adrenalectomy for a metastatic lesion diagnosed 4 years after nephrectomy performed for renal cell carcinoma of the contralateral kidney. Five years following the adrenalectomy the patient underwent leg amputation because of a solitary bone metastasis.

A rare simultaneous presentation of testicular mixed germ cell tumor with a contralateral testis torsion.

We report a rare case of a 27-year-old man presenting with an acute scrotum with simultaneous occurrence of testicular tumor and contralateral torsion. Preoperative imaging demonstrated the testicular missed torsion, yet findings were equivocal with regard to the testicular tumor. On scrotal exploration the left testis was found to be ischemic due to threefold rotation. The right testis was not identifiable, being composed of numerous necrotic lesions. Frozen section suggested malignancy, hence high right orchiectomy was performed. Histologic examination of the right testis showed mixed germ cell tumor, containing all the subtypes. To our knowledge no similar case has been reported.

Urinary cytokeratin 20 as a marker for transitional cell carcinoma.

OBJECTIVES: To determine if detection of cytokeratin 20 (CK20) gene expression, by reverse transcriptase-polymerase chain reaction (RT-PCR) in urine from transitional cell carcinoma (TCC) patients, can provide a new noninvasive tool for the follow-up of patients with urothelial carcinoma of the bladder. METHODS: Urine was collected from 95 patients previously diagnosed as TCC during their follow-up, and from 27 healthy volunteers. All patients had a transurethal resection of tumor or biopsies obtained from 'suspicious' areas in the bladder. RNA was extracted from cells collected from the urine and RT-PCR was performed with specific primers for the amplification of cytokeratin 8, a general marker for epithelial cells, and of CK 20, a marker for TCC urothelium. RESULTS: CK20 expression was detected in 86.7% of TCC patients, and only in 3.3% of healthy volunteers (specificity 96.7%). Strong correlation was found between tumor grade and expression of CK20 in urine. All grade III and IV tumors demonstrated positive CK20 expression (100% sensitivity), whereas the sensitivity for lower grades was between 71 and 80%. Among 11 patients with a previous biopsy-proven diagnosis of TCC and a current negative biopsy, in 9 patients CK20 expression was detected. Further follow-up of these patients for a period of 6 months revealed recurrence of TCC in 4 patients. CONCLUSION: CK20 detection in urine cells is a simple, noninvasive method with a high potential to become the marker of choice for monitoring and follow-up of TCC patients. More information is needed regarding CK20 expression in nonmalignant urological disease, to evaluate its use for routine screening purposes.

Leiomyosarcoma of the spermatic cord: report of two cases and review of the literature.

Two cases of spermatic cord leiomyosarcoma are described. Preoperative ultrasound disclosed a paratesticular tumor. Inguinal orchiectomy was performed; there was no adjuvant treatment. Currently there is no evidence of disease after 12 and 24 months of follow-up. The literature on this rare condition is reviewed.

Tetra-amelia with multiple malformations in six male fetuses of one kindred.

An Arab Moslem kindred is reported in which six abnormal male fetuses were born in three closely related sibships. They had amelia, malformed head and other severe skeletal and visceral malformations. The similarities and differences between the developmental and inherent characteristics found in our patients and in families with Roberts syndrome are discussed.

Cytotoxic phenotype of intra-epithelial lymphocytes in normal and cryptorchid human testicular excurrent ducts.

BACKGROUND: Most testicular and epididymal lymphocytes express T-cell markers, but their cytotoxic potential and activation status have not been reported. In this study, distribution of the cytotoxic cells was compared between normal and cryptorchid testes stratified into two groups: the first with complete absence of germ cells [Sertoli cell-only (SCO)] and the second with arrested spermatogenesis (SCA). METHODS: Immunohistochemistry for the T-lymphocyte marker CD3 and cytotoxic markers CD8, TIA-1 and granzyme B was performed on paraffin-embedded sections. RESULTS: The number of CD8+ and CD3+ intra-epithelial lymphocytes (IELs) increased distally throughout the normal epididymis. TIA-1 immunostaining revealed that a significant proportion of IELs exhibited cytotoxic potential, whereas granzyme B staining disclosed a subpopulation of activated cytotoxic lymphocytes (CTLs). TIA-1/CD8 and granzyme B/CD8 double immunostaining revealed that the vast majority of TIA-1+ and granzyme B+ cells were CD8+. The proportion of activated granzyme B+ lymphocytes increased distally throughout the normal epididymis. The number of TIA-1+ and granzyme B+ intra-epithelial and stromal lymphocytes was significantly increased in the normal as opposed to the SCO cryptorchid epididymis and proximal vas deferens. CONCLUSIONS: These results suggest that exposure of the testicular excurrent ducts to spermatozoa or immature germ cells triggers the activation and recruitment of CTLs. Cytotoxic granule effector mechanisms may contribute to the immunological barrier preventing the immune response to spermatozoa in testicular ducts.

Telomerase activity in patients with transitional cell carcinoma: a preliminary study.

BACKGROUND: Telomerase activity is not detectable in normal cells, and their telomers shorten until the chromosome is unable to replicate. Immortal cells have short but stable chromosomes and increased telomerase activity. Transitional cell carcinoma (TCC) has only a few useful markers of diagnostic or prognostic importance. The objective of this study was to determine whether there was a correlation between telomerase activity and the grade or stage of TCC, and whether the enzyme's activity could serve as a biochemical marker of this tumor. METHODS: The study included 29 patients with TCC. From each patient, samples of urine cells were obtained, and a cup biopsy was taken from an apparently normal area as well as from a part of the bladder tumor resected transurethrally. Control uroepithelial biopsies were taken from normal transitional cell sites from non-TCC patients. Biopsies or cells were subjected to either histologic examination or telomerase activity determination. RESULTS: Twenty-six of 29 (90%) of the tumor biopsies exhibited telomerase activity. Most of the cup biopsies were categorized as metaplastic or dysplastic, and 20 of 29 (69%) of these exhibited telomerase activity. Telomerase activity was found in 17 of 21 (81%) of the urine cells but in only 3 of 14 (21%) of control urine cells. All (10 of 10) of the uroepithelial biopsies taken from non-TCC patients did not show any telomerase activity. CONCLUSIONS: In this study, almost all tumor biopsies exhibited telomerase activity. The high incidence of telomerase activity found in cup biopsies of the malignant field uroepithelial cells from cup biopsies of TCC patients may suggest that telomerase could be activated early in carcinogenesis. A high incidence of telomerase activity was found in voided uroepithelial cells of TCC patients; however, no correlation between this activity and the histologic determination of grading and staging of the tumor was found.