Percentage of embryonal carcinoma and of vascular invasion predicts pathological stage in clinical stage I nonseminomatous testicular cancer.

We analyzed 92 clinical stage I nonseminomatous testicular germ cell tumors for primary tumor histological factors that would distinguish true pathological stage I disease (N = 54) from those patients who harbored occult disease and actually were later found to have pathological stage II disease (N = 38). Primary tumor pathological material was analyzed for vascular invasion, lymphatic invasion, tunical invasion, and quantitative determination of percentage of the primary tumor composed of embryonal carcinoma, yolk sac carcinoma, teratoma, and seminoma. Univariate logistic regression analyses revealed that vascular invasion (P = 0.0001), percentage of embryonal carcinoma (P = 0.0001), lymphatic invasion (P = 0.0001), and tunical invasion (P = 0.0013) were higher in pathological stage II and that percentage of teratoma (P = 0.0001) and of yolk sac carcinoma (P = 0.0174) were higher in stage I. Percentage of seminoma was not significant. Individually, these parameters were able to correctly predict occult disease 66.3 to 80.4% of the time. In multivariate logistic regression analysis, only vascular invasion and percentage of embryonal carcinoma remained significant, and a model using these two variables was able to correctly predict stage 85.9% of the time. Vascular invasion and determination of percentage of embryonal carcinoma should be assessed for all clinical stage I nonseminomatous germ cell tumor patients and the model presented herein can be used clinically to predict the likelihood of occult disease and dictate therapy.

Efficacy of radiographic chest imaging in patients with testicular cancer.

OBJECTIVE: To determine the efficacy of computed tomography of the chest (CTC) and plain radiograph (CXR) in the initial staging process of testicular germ cell tumors. METHODS: The medical records of 362 patients with testicular germ cell tumor treated at our center between January 1980 and August 1993 were reviewed with particular attention to initial chest screening studies. Two hundred one patients had both CXR and CTC, 24 CXR alone, and 20 CTC alone during initial staging. One hundred seventeen patients were excluded from analyses because of undergoing whole lung tomography (92), unknown staging (19), or inadequate follow-up (6). Analysis included findings based on abdominal staging results using computed tomography of the abdomen (CTA). RESULTS: Of the 201 patients who had both CTC and CXR, 117 (58.2%) had nonseminomas (NSGCT) and 84 (41.8%) had seminomas (SEM). Among the patients with NSGCT, 21 (17.9%) had chest metastasis, 16 (76.2%) of which were detected by CXR. The 5 that were missed on CXR had significant retroperitoneal disease documented by CTA and the knowledge of chest metastases potentially altered therapy in 2 patients. Only 2 of 84 (2.4%) patients with SEM had metastatic chest disease and both were identified by CXR. False-positive CTC following negative CXR resulted in costly and sometimes invasive additional procedures in 10 patients with NSGCT and 6 with SEM. None of the CXR-only patients had adverse consequences from the solitary study (at least 1 year follow-up). The CTC-only patients could have undergone CXR only and had similar outcome. CONCLUSIONS: CXR alone is preferable for initial chest staging in all patients with SEM and in patients with NSGCT with negative findings on CTA. CTC remains of slight benefit for patients with clinical Stage II and greater NSGCT and to evaluate further suspicious CXR findings in any patient, although it appears not to be necessary in patients who have clinical Stage I disease determined by CTA. These findings have important cost-saving implications.

Retroperitoneal imaging with third and fourth generation computed axial tomography in clinical stage I nonseminomatous germ cell tumors.

OBJECTIVES: To examine the accuracy rate of abdominal staging using third and fourth generation computed tomography (CT) scanning in clinical Stage I testicular nonseminoma patients. METHODS: Between January 1985 and August 1993, 57 patients presented to our center with clinical Stage I testicular nonseminoma. Retroperitoneal computed tomographic staging studies were interpreted to be normal preoperatively in the entire group. In addition, tumor marker values were normal or returned to normal postorchiectomy within the appropriate half-life intervals. All patients were subjected to radical or modified retroperitoneal lymph node dissection (19% and 72%, respectively). Original abdominal CT scans (preretroperitoneal lymph node dissection) were available for blinded retrospective re-review in 16 cases (7 pathologic Stage II, 9 pathologic Stage I). RESULTS: Nineteen of 57 (33%) patients were upstaged at surgery including 6 patients (11%) who demonstrated II B volume disease. Third and fourth generation CT scanning of the retroperitoneum yielded a 66% accuracy rate in this population. Six out of 7 pathologic Stage II pre-lymph node dissection abdominal CT scans that were available for blinded re-review revealed nonpathologic nodes by size criteria in the primary landing zone for the corresponding original tumor. CONCLUSIONS: Our data suggests that for clinical Stage I nonseminoma in the 1985 to 1993 era, undue reliance was placed on a less than ideal staging test. The 33% false-negative rate reported showed no improvement over earlier reports and reaffirms concern for relying solely on third or fourth generation CT imaging of the retroperitoneum in the staging of clinical Stage I nonseminomatous germ cell tumor (NSGCT) patients. The presence of any number of lymph nodes in the expected primary landing zone, regardless of size, should raise serious suspicion for occult nodal disease.

Inverted Y duplication of the ureter associated with a distal limb ectopic to the seminal vesicle.

Inverted Y duplication of the ureter is a rare anomaly. We report on a 24-year-old man who presented with urolithiasis and azoospermia in a solitary functioning kidney with an inverted Y ureteral duplication. To our knowledge our case represents the first documentation of ectopic emptying of 1 limb of the inverted Y ureter into the seminal vesicle. The embryology and management of this complex case are discussed.

Neural network analysis of quantitative histological factors to predict pathological stage in clinical stage I nonseminomatous testicular cancer.

A great deal of controversy exists in staging clinical stage I (CSI) nonseminomatous testicular germ cell tumors (NSGCT) because of the difficulty of distinguishing true stage I patients from those with occult retroperitoneal or distant metastases. The goal of this study was to quantitate primary tumor histologic factors and to apply these in a neural network computer analysis to determine if more accurate staging could be achieved. All available primary tumor histological slides from 93 CSI NSGCT patients were analyzed for vascular invasion (VI), lymphatic invasion (LI), tunical invasion (TI) and quantitative determination of percentage of the primary tumor composed of embryonal carcinoma (%EMB), yolk sac carcinoma (%YS), teratoma (%TER) and seminoma (%SEM). These patients had undergone retroperitoneal lymphadenectomy or follow-up such that final stage included 55 pathologic stage I and 38 stage II or higher lesions. Two investigators were provided identical datasets for neural network analysis; one experienced researcher used custom Kohonen and back propagation programs and one less experienced researcher used a commercially available program. For each experiment, a subset of data was used for training, and subsets were blindly used to test the accuracy of the networks. In the custom back propagation network, 86 of 93 patients were correctly staged for an overall accuracy of 92% (sensitivity 88%, specificity 96%). Using Neural Ware commercial software 74 of 93 (79.6%) were accurately staged when all 7 input variables were used; however, accuracy improved from 84.9 to 87.1% when 2, 4 and 5 of the variables were used. Quantitative histologic assessment of the primary tumor and neural network processing of data may provide clinically useful information in the CSI NSGCT population; however, the expertise of the network researcher appears to be important, and commercial software in general use may not be superior to standard regression analysis. Prospective testing of expert methodology should be instituted to confirm its utility.

Thymic hyperplasia in newly diagnosed testicular germ cell tumors.

Thymic hyperplasia has been reported as a rebound phenomenon in children and young people, most commonly following chemotherapy for cancer. Although thymic hyperplasia has been documented in testis cancer patients after chemotherapy, to our knowledge it has not previously been reported in newly diagnosed cases before systemic therapy. A retrospective review of 362 testicular germ cell tumor patients treated at a single tertiary care center between January 1, 1980 and August 1, 1993 was performed, with special review of 221 who underwent computerized tomography staging of the chest. Thymic hyperplasia was detected in 4 of the 221 patients (1.8%) including 3 of 100 (3.0%) with seminoma and 1 of 121 (0.8%) with nonseminoma. All 4 patients had low stage (I or IIa) disease with a delay in diagnosis (5 to 24 weeks) and thymic hyperplasia was discovered at staging evaluation 18 to 37 days after orchiectomy but before other cancer therapy was administered. Of the 4 patients 2 underwent thymectomy, revealing histological thymic rebound hyperplasia. All 4 patients had no evidence of recurrence at 1 to 54 months after treatment. In addition to the well known post-chemotherapy phenomenon, thymic hyperplasia may also occur in nonsystemically treated, newly diagnosed testicular cancer patients. An anterior mediastinal mass in an otherwise low stage newly diagnosed testicular cancer patient may represent thymic hyperplasia and not necessarily metastatic disease.

Proliferating cell nuclear antigen expression to predict occult disease in clinical stage I nonseminomatous testicular germ cell tumors.

We analyzed primary tumor tissue from 89 clinical stage I nonseminomatous germ cell testicular tumor patients for proliferating cell nuclear antigen expression and histological features to determine if these elements could distinguish pathological stage I (52 patients) from pathological stage II disease or patients who later had relapse (37). Using a monoclonal antibody (PC10) developed for use in archival tissue, nuclear proliferating cell nuclear antigen expression was immunohistochemically measured for the overall tumor (total proliferating cell nuclear antigen) and for each neoplastic cell type present. In addition, the primary tumor was examined for the presence of vascular invasion and determination of the percentage of tumor composed of embryonal carcinoma. Univariate logistic regression analysis revealed higher total (p = 0.0001) and higher embryonal carcinoma proliferating cell nuclear antigen expression (p = 0.0437) to be statistically significant risk factors for occult disease, correctly predicting its presence 73% and 61.5% of the time, respectively. More importantly, the presence of vascular invasion and a higher percentage embryonal carcinoma were highly significant risk factors for occult disease and were truly predictive in 80.4% and 77.2% of the cases, respectively. Multivariate logistic regression analysis revealed a combination of vascular invasion and percentage embryonal carcinoma to be the best model to predict occult disease correctly (85.9%). The addition of total or embryonal carcinoma proliferating cell nuclear antigen expression did not improve the clinical use of the model containing vascular invasion and percentage embryonal carcinoma. Although proliferating cell nuclear antigen expression mirrors the biological behavior of clinical stage I nonseminomatous germ cell testicular tumor to some degree, assessment of vascular invasion and percentage embryonal carcinoma has greater clinical use.