Positron emission tomography scans in postchemotherapy seminoma patients with residual masses: a retrospective review from Indiana University Hospital.
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Diagnosis, Differential↗
Biomedical subjects
Richard S Foster
Publications and source records attributed to Richard S Foster.
Interphase fluorescence in situ hybridization analysis of chromosome 12p abnormalities is useful for distinguishing epidermoid cysts of the testis from pure mature teratoma.
PURPOSE: The distinction of epidermoid cyst of the testis from teratoma is of critical importance because the former is benign and the latter is a malignant tumor that may have associated metastasis of either teratomatous or non-teratomatous germ cell tumor types. Chromosome 12p abnormalities are seen in the vast majority of testicular germ cell tumors of adults and are present in all histologic subtypes. In this study, we investigated the clinical utility of interphase fluorescence in situ hybridization (FISH) analysis of chromosome 12p abnormalities for distinguishing epidermoid cysts of the testis from pure mature teratoma. EXPERIMENTAL DESIGN: Sixteen testicular epidermoid cysts and 17 testicular teratomas were investigated for isochromosome 12p [i(12p)] and 12p overrepresentation using interphase FISH analysis. RESULTS: Neither i(12p) nor 12p overrepresentation were observed in 16 epidermoid cyst cases, whereas i(12p) was detected in 76% of teratomas and 12p overrepresentation was identified in 29% of teratomas. Overall, 88% of testicular teratomas had chromosome 12p abnormalities. CONCLUSIONS: FISH identification of i(12p) and/or 12p overrepresentation in routinely processed surgical specimens is a useful ancillary diagnostic tool in distinguishing testicular epidermoid cysts from teratoma.
Adolescent↗
Clonal origin of metastatic testicular teratomas.
PURPOSE: Testicular teratomas in adult patients are histologically diverse tumors that frequently coexist with other germ cell tumor (GCT) components. These mixed GCTs often metastasize to retroperitoneal lymph nodes where multiple GCT elements are frequently present in the same metastatic lesion. Neither the genetic relationships among the different components in metastatic lesions nor the relationships between primary and metastatic GCT components have been elucidated. EXPERIMENTAL DESIGN: We examined metastases from 31 patients who underwent primary retroperitoneal lymph node dissection for metastatic testicular GCT. All patients had metastatic mature teratoma with one or more other GCT components. This study included a total of 72 metastatic GCT components and 16 primary GCT components from 31 patients. Genomic DNA samples from each component were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-assisted microdissection. Loss of heterozygosity (LOH) assays for seven microsatellite polymorphic markers on chromosomes 1p36 (D1S1646), 9p21 (D9S171 and IFNA), 9q21 (D9S303), 13q22-q31 (D13S317), 18q22 (D18S543), and 18q21 (D18S60) were done to assess clonality. RESULTS: Twenty-nine of 31 (94%) cases showed allelic loss in one or more components of the metastatic GCTs. Twenty-nine of 31 mature teratomas showed allelic loss in at least one of seven microsatellite polymorphic markers analyzed. The frequency of allelic loss in informative cases of metastatic mature teratoma was 27% (8 of 30) with D1S1646, 34% (10 of 29) with D9S171, 37% (10 of 27) with IFNA, 27% (8 of 30) with D9S303, 46% (13 of 28) with D13S317, 26% (7 of 27) with D18S543, and 36% (10 of 28) with D18S60. Completely concordant allelic loss patterns between the mature teratoma and all of the other metastatic GCT components were seen in 26 of 29 cases in which the mature teratoma component showed LOH. Nearly identical allelic loss patterns were seen in the three remaining cases. In six cases analyzed, LOH patterns of each metastatic component were compared with each GCT component of the primary testicular tumor. In all six cases, each primary and metastatic component showed an identical pattern of allelic loss. CONCLUSION: Our data support the common clonal origin of metastatic mature teratomas with other components of metastatic testicular GCTs and with each component of the primary tumor.
Adolescent↗
Predicting retroperitoneal histology in postchemotherapy testicular germ cell cancer: a model update and multicentre validation with more than 1000 patients.
OBJECTIVES: Surgical resection of postchemotherapy retroperitoneal lymph nodes is often performed in patients with advanced nonseminomatous testicular germ cell cancer. We previously developed a model to predict the probability that the lymph nodes contain only necrotic or fibrotic (benign) tissue versus mature teratoma and viable cancer (tumour) to identify patients who actually need resection. The present study used an updated model with new patient data and studied the validity of the updated model across various settings. METHODS: We combined data of 544 patients from the original model with data of 550 new patients and performed a new logistic regression analysis, which included the same six predictors: histology of the primary tumour, prechemotherapy serum levels of alpha-fetoprotein, human chorionic gonadotropin, lactate dehydrogenase, residual mass size measured on computed tomography, and change in mass size. The validity of the updated model was studied in individual centres. Calibration of the predicted probabilities was assessed graphically and with the Hosmer-Lemeshow test. Discrimination was studied with the concordance (c)-statistic. RESULTS: The updated model had slightly different, although more precise, regression coefficients. Statistically nonsignificant Hosmer-Lemeshow tests confirmed good calibration in most centres. The c-statistic for all centres except one exceeded 0.80. The updated model was valid over the complete range of predicted probabilities across a broad spectrum of centres. CONCLUSIONS: This finding gives confidence in the applicability of the model to select patients for resection, particularly patients with small residual masses and low predicted probabilities of benign tissue (i.e., substantial predicted risks of residual tumour).
Humans↗
Bleomycin, etoposide, and cisplatin for three cycles compared with etoposide and cisplatin for four cycles in good-risk germ cell tumors: is there a preferred regimen?
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Antineoplastic Combined Chemotherapy Protocols↗
Long-term outcome of retroperitoneal lymph node dissection in the management of testis cancer.
In low volume testicular cancer, (clinical stage A/B1) retroperitoneal lymph node dissection has maintained its therapeutic benefit while minimizing morbidity with the reduction of the surgical template from a full bilateral dissection to a unilateral nerve-sparring surgery. The optimal treatment for low stage disease is largely patient driven with surgery and surveillance considered the primary treatment modalities. In the post chemotherapy population, patients with complete radiographic resolution of retroperitoneal disease are observed at Indiana University as the relapse rate in this population is approximately 5%. Residual masses after chemotherapy should be resected. A modified post chemotherapy dissection is adequate in low volume disease restricted to the primary landing zone of the affected testicle. In chemo-refractory disease, aggressive surgery provides a 5 year survival of 31% for patients with active cancer. Excluding chemo-naïve patients, late relapse disease is managed surgically with 50% being cured of disease.
Combined Modality Therapy↗
OCT4 is superior to CD30 in the diagnosis of metastatic embryonal carcinomas after chemotherapy.
Correctly diagnosing a metastatic germ cell tumor after chemotherapy may be challenging because of the diverse morphological manifestations of postchemotherapy tumors. Both OCT4 and CD30 are sensitive markers for the identification of primary embryonal carcinomas; however, loss of expression of CD30 (65%) has been reported in metastatic embryonal carcinomas after chemotherapy. The present study was conducted to evaluate the expression patterns of OCT4 and CD30 in postchemotherapy metastatic embryonal carcinomas and to compare their utility as diagnostic tools. Twenty-five cases of metastatic embryonal carcinoma after chemotherapy were immunohistochemically analyzed for CD30, OCT4, and cytokeratin AE1/AE3 expression. The staining intensities and the percentages of positively staining tumor cells were recorded. Nineteen (76%) of 25 cases revealed diffuse, moderate to strong nuclear OCT4 staining in postchemotherapy embryonal carcinomas. Among these 19 OCT4-positive cases, 8 also revealed diffuse and moderate to strong membranous CD30 staining. Seven of these OCT4-positive cases retained focal and weak CD30 expression. The remaining 4 OCT4-positive cases demonstrated a complete loss of CD30 expression. The 19 OCT4-positive cases showed a positive but variable cytokeratin AE1/AE3 expression pattern. Six (24%) of 25 cases were negative for both CD30 and OCT4 but demonstrated diffuse and strong cytokeratin AE1/AE3 staining. OCT4 is a useful diagnostic marker to identify metastatic embryonal carcinomas after chemotherapy, with a better sensitivity than CD30.
Adult↗
Outcome analysis for patients with elevated serum tumor markers at postchemotherapy retroperitoneal lymph node dissection.
PURPOSE: To evaluate the therapeutic benefit of postchemotherapy retroperitoneal lymph node dissection (PCRPLND) in patients with persistently elevated serum tumor markers. PATIENTS AND METHODS: One hundred fourteen patients with metastatic germ cell cancer with elevated serum tumor markers after first-line (50 patients) or second-line chemotherapy (64 patients) who underwent PCRPLND between 1977 and 2000 with a minimum follow-up of 2-years were included in this retrospective study. RESULTS: The 5-year overall survival was 53.9%. Sixty-one patients (53.5%) are alive with a medium follow-up of 72 months. Fifty-three patients died of disease, with a medium time to death of 8.0 months. Mean preoperative serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (betaHCG) levels were 483 ng/mL and 555 mU/mL, respectively, with no difference in 5-year survival (P = .2). Retroperitoneal pathology revealed germ cell cancer in 53.5% of patients, teratoma in 34.2% of patients, and fibrosis in 12.2% of patients, with 5-year survival rates of 31.4%, 77.5%, and 85.7%, respectively (P < .0001). Predictors of retroperitoneal pathology included an increasing serum AFP or betaHCG, betaHCG more than 100 ng/mL, redo retroperitoneal lymph node dissection (RPLND), and second-line chemotherapy. Poor prognostic variables by multivariable analysis included betaHCG status, serum AFP level, redo RPLND, and germ cell cancer in the resected specimen. CONCLUSION: A subset of patients with elevated serum tumor markers after chemotherapy is curable with surgery. The prognostic factors predictive of outcome in this analysis include an increasing betaHCG, serum AFP level, redo RPLND, and germ cell cancer in the resected specimen. These factors, along with clinical and surgical experience, should aid in determining the appropriate integration of surgery and chemotherapy in this population.
Biomarkers, Tumor↗
The combined percentage of Gleason patterns 4 and 5 is the best predictor of cancer progression after radical prostatectomy.
PURPOSE: Clinical outcome is variable in prostate cancer patients treated with radical prostatectomy. The Gleason histologic grade of prostatic adenocarcinoma is one of the strongest predictors of biologic aggressiveness of prostate cancer. We evaluated the significance of the relative proportion of high-grade cancer (Gleason patterns 4 and/or 5) in predicting cancer progression in prostate cancer patients treated with radical prostatectomy. PATIENTS AND METHODS: Radical prostatectomy specimens from 364 consecutive prostate cancer patients were totally embedded and whole mounted. Various clinical and pathologic characteristics were analyzed. All pathologic data, including Gleason grading variables, were collected prospectively. RESULTS: A multiple-factor analysis was performed that included the combined percentage of Gleason patterns 4 and 5, Gleason score, tumor stage, surgical margin status, preoperative prostate-specific antigen (PSA), extraprostatic extension, and total tumor volume. Using Cox regression analysis with bootstrap resampling for predictor selection, we identified the combined percentage of Gleason patterns 4 and 5 (P < .0001) and total tumor volume (P = .009) as significant predictors of PSA recurrence. CONCLUSION: The combined percentage of Gleason patterns 4 and 5 is one of the most powerful predictors of patient outcome, and appears superior to conventional Gleason score in identifying patients at increased risk of disease progression. On the basis of our results, we recommend that the combined percentage of Gleason patterns 4 and 5 be evaluated in radical prostatectomy specimens. The amount of high-grade cancer in a prostatectomy specimen should be taken into account in therapeutic decision making and assessment of patient prognosis.
Adenocarcinoma↗
Impact of the number of positive lymph nodes on disease-free survival in patients with pathological stage B1 nonseminomatous germ cell tumor.
PURPOSE: The prognostic significance of the number of metastatic lymph nodes detected at surgery on survival is well documented for breast and colon cancer, and it has recently been reported in bladder cancer. We tested this hypothesis in patients with pathological stage B1 nonseminomatous germ cell tumor (NSGCT). MATERIAL AND METHODS: This series included 118 patients with pathological stage B1 NSGCT (5 or fewer positive lymph nodes) at primary retroperitoneal lymph node dissection who did not receive adjuvant chemotherapy at a followup of greater than 24 months. RESULTS: Five-year disease-free survival (DFS) was 68% at a median followup of 43 months. Median followup in patients without recurrence was 67.4 months and median time to recurrence was 5.0 months. The mean and median number of positive lymph nodes was 2.0. Five-year DFS for 1 or 2 and 3 to 5 positive lymph nodes was 72% and 59%, respectively (p = 0.0847). Five-year DFS for lymph node density less or greater than 0.05 was 75% and 66%, respectively (p = 0.261). Neither the number of positive lymph nodes (continuous and categorical p = 0.201 and 0.271) or the ratio of the number of positive lymph nodes to the total number resected (continuous and categorical p = 0.415 and 0.998, respectively) predicted recurrence. CONCLUSIONS: Primary retroperitoneal lymph node dissection is curative in patients with pathological stage B1 NSGCT and DFS does not seem to be influenced by the number or the ratio of positive lymph nodes resected. This information may be helpful in limiting adjuvant chemotherapy in patients otherwise cured by surgery.
Disease-Free Survival↗
Does the histology of nodal metastasis predict systemic relapse after retroperitoneal lymph node dissection in pathological stage B1 germ cell tumors?
PURPOSE: We evaluated the prognostic significance of the histology of metastatic lymph nodes to predict postoperative relapse in pathological stage B1 nonseminomatous germ cell tumor (NSGCT). MATERIALS AND METHODS: A retrospective review of the testicular cancer database was performed to identify all patients with clinical stage A NSGCT who underwent primary retroperitoneal lymph node dissection and were found to have pathological stage B1 disease. No patient received adjuvant chemotherapy and minimal followup was 24 months. RESULTS: A total of 118 patients were identified with a 5-year disease-free survival (DFS) of 68% and a median followup of 43 months. Embryonal cell carcinoma was identified in 92 of 118 (77%) surgical specimens, which was significantly greater than the presence of teratoma (22%), seminoma (16%) and yolk sac (14.4%, p < or = 0.001) with no difference in 5-year DFS comparing the presence or absence of each histology. Solitary histology was noted in 88 of 118 patients (74.5%). Embryonal cell carcinoma was the most common single histology identified at surgery at 64 of 88 (73%), with the incidence of seminoma, teratoma and yolk sac being 12.5%, 9.0% and 5.5%, respectively (p < or = 0.001). There was no statistical difference in DFS for each of the solitary histological subtypes (p=0.67). Recurrence rates were similar for pure embryonal cell carcinoma (69%), mixed embryonal cell carcinoma (63%) and no embryonal cell carcinoma (73%) in the retroperitoneum (p=0.63). CONCLUSIONS: Retroperitoneal histology does not appear to predict outcome in patients with pathological stage B1 NSGCT.
Carcinoma, Embryonal↗
Gene expression profiling of early- and late-relapse nonseminomatous germ cell tumor and primitive neuroectodermal tumor of the testis.
PURPOSE: To better understand the molecular mechanisms that underlay the development and progression of nonseminomatous germ cell tumor of testis (NSGCTT) as well as malignant transformation of teratoma and primitive neuroectodermal tumor (PNET). EXPERIMENTAL DESIGN: We studied the gene expression profiles of 17 retroperitoneal NSGCTTs (10 yolk sac tumors, 3 embryonal carcinomas, 4 teratomas) and 2 PNETs obtained from patients with two clinical outcomes. Tissue samples were obtained from the Indiana University. One group of NSGCTT and PNET patients developed metastases within 2 years (early-relapse) of initial successful treatment, and the other group developed metastases after 2 years (late-relapse). Gene expression in these groups of patients was quantified using cDNA microarrays and real-time relative quantitative PCR. RESULTS: We demonstrate that the gene expression profiles of these tumors correlate with histological type. In addition, we identify type-specific genes that may serve as novel diagnostic markers. We also identify a gene set that can distinguish between early-relapse and late-relapse yolk sac tumors. The expression differences of these genes may underlie the differences in clinical outcome and drug response of these tumors. CONCLUSION: This is the first study that used gene expression profiling to examine the molecular characteristics of the NSGCTTs and drug response in early- and late-relapse tumors. These results suggest that two molecularly distinct forms of NSGCTTs exist and that the integration of expression profile data with clinical parameters could enhance the diagnosis and prognosis of NSGCTTs. More importantly, the identified genes provide insight into the molecular mechanisms of aggressive NSGCTTs and suggest intervention strategies.
Cell Transformation, Neoplastic↗
Secondary surgery in germ cell tumors--when and how extensively should it be performed?
Postchemotherapy RPLND has been used for several decades. Two current issues relating to this surgery are discussed in this article. The selection for surgery and the extent of surgery to be performed continue to evolve.
Combined Modality Therapy↗
Nephroblastoma arising in a germ cell tumor of testicular origin.
We report a nephroblastoma arising in a germ cell tumor of testicular origin occurring in a 22-year-old man. Orchiectomy demonstrated a malignant mixed germ cell tumor composed of mature and immature teratoma with nephroblastoma and rhabdomyosarcoma. Following chemotherapy, the patient developed supraclavicular and retroperitoneal lymphadenopathy. Excision demonstrated metastatic teratoma at both sites. No recurrence was noted with 21 months of additional follow-up. Using tissue microdissection and loss of heterozygosity analysis, we investigated the clonality of the mature teratoma, immature teratoma, nephroblastoma, and rhabdomyosarcoma components of the primary tumor and of the metastatic mature teratoma at the two separate distant sites. Nine microsatellite polymorphic makers were used to examine the pattern of allelic loss in both primary and metastatic tumors. Loss of heterozygosity was found in 4 DNA loci, and the same pattern of allelic loss was demonstrated at all 4 loci in all of the different components of the primary tumor and the metastatic mature teratomas, supporting the germ cell tumor origin of the nephroblastoma component. Loss of heterozygosity on chromosome 17p13 (TP53) was detected in metastatic mature teratoma, but not in the primary tumor. Loss of heterozygosity was observed at 11p13, the locus of WT1 inactivation in patients genetically predisposed to nephroblastoma, and this loss may be an important genetic mechanism in nephroblastomatous differentiation of germ cell tumors. These data support a common clonal origin for nephroblastoma and the other germ cell tumor components.
Adult↗
Histology in mixed germ cell tumors. Is there a favorite pairing?
PURPOSE: Mixed germ cell tumors account for approximately 30% to 50% of testicular tumors. To our knowledge a systematic review with statistical analysis of the associations of histological subtypes in mixed germ cell tumors has not been done previously. It was our impression that such associations exist. Delineating concordant histological types may provide insight into the ontogeny of testicular tumors and also have important clinical implications. MATERIALS AND METHODS: We retrospectively reviewed the testis cancer data base at our institution. The primary tumor of orchiectomy specimens was examined in 2589 patients. Of these patients mixed histology was noted in 1765 (68.2%). ORs were calculated for all possible combinations of teratoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma and seminoma. In addition, we evaluated the association of various histological types with teratoma at post-chemotherapy retroperitoneal lymph node dissection. RESULTS: Of 10 possible combinations of histological types in the primary tumor, positive correlations were noted in 4. The strongest correlation was found between teratoma and yolk sac tumor (OR 2.58, p <0.001). Teratoma or yolk sac tumor in the testis was associated with teratoma in the pathology specimen at post-chemotherapy retroperitoneal lymph node dissection. CONCLUSIONS: The strongest associations of histological subtypes in mixed germ cell tumors were seen between yolk sac tumor and teratoma. Similar associations are seen in late relapse and in some cases of prepubertal tumors. Further study of these associations may prove valuable in understanding the biology and clinical behavior of germ cell tumors.
Germinoma↗
Complications of post-chemotherapy retroperitoneal lymph node dissection for testis cancer.
PURPOSE: Post-chemotherapy retroperitoneal lymph node dissection (PC RPLND) is a tool in the management of testis cancer. Our impression has been that the short-term morbidity of standard PC RPLND has diminished with time. Therefore, we attempted to verify this hypothesis by evaluating the morbidity of the procedure in 2 comparable groups of patients from 2 different periods. MATERIALS AND METHODS: We compared 150 patients who underwent post-chemotherapy RPLND between July 2000 and July 2002 to 79 patients who underwent the same procedure between 1990 to 1992. All patients had clinical stage II-III testis cancer and had received 3 to 4 courses of standard platinum based chemotherapy before surgery. We compared surgical morbidity and postoperative complications in both groups. We also assessed a number of factors (patient characteristics, mass size, pathological features and surgical aspects) that could impact the rate of complications. RESULTS: The 2 groups were comparable regarding preoperative clinical stage, patient characteristics and postoperative pathological findings. PC RPLND procedures were performed using the same technique. Compared to patients in the 1990 to 1992 group, the patients from the 2000 to 2002 group had fewer intraoperative complications and additional procedures (44 [29.3%] of 150 versus 41 [51.9%] of 79, p = 0.0008), a trend toward a lower postoperative complication rate (10 [6.7%] compared to 11 [13.9%], p = 0.07) and shorter hospital stay (average 5.6 versus 8.4 days [p <0.0001]). CONCLUSIONS: With time morbidity and hospital stay after standard PC RPLND have decreased. This finding probably reflects differences in patterns of care rather than changes in surgical technique. Therefore, comparing newer surgical techniques to historical controls is inappropriate since differences may not actually represent the technical advances of the newer procedure.
Humans↗
Cystic trophoblastic tumor: a nonaggressive lesion in postchemotherapy resections of patients with testicular germ cell tumors.
Cystic trophoblastic tumor (CTT) is an uncommon lesion that is usually seen after chemotherapy in patients with testicular germ cell tumors. Its clinical significance has not been well studied. We identified 17 patients with CTT in retroperitoneal lymph node dissections (RPLNDs) after cisplatin-based chemotherapy for testicular germ cell tumors. None had other forms of persistent germ cell tumor except for teratoma, and no patient received additional chemotherapy after RPLND. At the time of RPLND, 7 patients were known to have had normal serum levels of beta-subunit of human chorionic gonadotropin (beta-hCG), whereas 5 had relatively mild elevations (1.6-165 mIU/mL, median, 8.0 mIU/mL). The CTTs consisted of circumscribed, small cysts, usually multifocal, lined by mostly mononucleated trophoblast cells with abundant eosinophilic cytoplasm, often with smudged nuclei and showing only infrequent mitotic figures. Although the epithelial lining was often stratified to several layers in thickness or formed intracystic papillary tufts, solid proliferations of trophoblast cells within the stroma were absent, as were clearly biphasic admixtures of mononucleated and multinucleated trophoblast cells. The cysts were either empty or contained fibrinoid material and were set in a hypocellular, fibrous stroma with adjacent teratoma. Stains for hCG highlighted rare cells. On follow-up of 15 patients, 11 were disease free (mean, 80 months). Three recurred with serum alpha-fetoprotein elevations at 25, 31, and 107 months, respectively, and one with beta-hCG elevation at 2 months. The latter patient, however, also had unresected mediastinal tumor postchemotherapy. We conclude that the finding of CTT in postchemotherapy resections does not warrant additional chemotherapy. Its clinical significance appears similar to that of residual teratoma.
Adolescent↗
Modified retroperitoneal lymphadenectomy.
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Anatomy, Artistic↗