Pure Teratoma Research Articles

Immunohistochemical detection of p63 in testicular germ cell neoplasia

p63 is a novel transcription factor-encoding gene with sequence homology to p53. p63 proteins have epithelial stem-cell regulatory functions and play a critical role in tissue development. Study of p63 expression in testicular germ cell tumors has been limited. Thirty-four archival cases of testicular germ cell neoplasia were examined and stained with monoclonal anti-p63 antibody 4A4 using standard methods. Included were 19 seminomas, 1 pure teratoma, 3 pure embryonal carcinomas, 1 pure yolk sac tumor, and 10 mixed germ cell tumors. p63 staining was consistently positive in teratomas in areas of squamous differentiation and in basal reserve-like cells in foci of respiratory/endodermal differentiation. Strong p63 staining was observed within cytotrophoblasts of choriocarcinoma (1/1), whereas focal positivity was detected in embryonal carcinomas (4/10) and yolk sac tumors (2/5). Seminomas and intratubular germ cell neoplasia were p63-negative. These findings may suggest the presence of pluripotent p63-positive stem cell-like nests in yolk sac tumors and embryonal carcinomas or may represent areas of an occult teratoma phenotype undetectable histopathologically on hemotoxylin-eosin sections. p63 positivity in cytotrophoblasts of choriocarcinoma is consistent with gynecologic studies, possibly reflecting the role of p63 in the oncogenesis of neoplastic trophoblasts. The consistent p63 negativity in seminomas may reflect a precommitted embryonic precursor-like phenotype.

Spontaneous Regression of Testicular Germ Cell Tumors

Spontaneous regression of testicular germ cell tumors (GCTs) is a well-recognized phenomenon but has been incompletely characterized. Many pathologists are not familiar with the findings that support a diagnosis of a "burnt-out" primary in a patient with metastatic GCT. We therefore report the clinical, gross, and histologic findings in 42 cases of testicular GCT that showed either complete (26) or greater than 50% scarring (16). Thirty-seven patients (88%) had either known GCT metastasis or some residual testicular GCT, and none had treatment before orchiectomy. The patients were 17 to 67 years old, with a median of 32. Thirty presented with symptoms of metastasis, 7 with a testicular mass, 2 with elevated human chronic gonadotropin, and 1 with testicular pain. In 2 patients the presentation was unknown. Two patients had prior orchiopexy; another had an intraabdominal testis, and 2 others had prior contralateral seminoma (20 and 42 years previously). Gross descriptions in 37 cases identified white to tan scars, 0.6 to 2.4 cm, in 33. These were circumscribed in 16, with 15 of these having nodular or multinodular configurations and 1 a band-like appearance. In 9 cases the scar was ill defined or stellate, and in 8 cases no further details concerning the scar configuration were available. In 4 cases no scar was apparent; 2 of these had received intraoperative biopsy. Microscopically, all cases showed circumscribed to irregular foci of scarring, distinct from the adjacent parenchyma, in association with widespread testicular atrophy. Other common features were lymphoplasmacytic infiltrates in the scars (37/42) and "ghost" tubules in scars (31/42). Less common features in the scars included angiomatous foci (22/42), siderophages (15/42), and coarse intratubular calcifications (6/42); in the surrounding testis they included intratubular germ cell neoplasia, unclassified (IGCNU) (22/42), Leydig cell prominence (18/42), and necrosis (5/42). Tubular microliths occurred in 13 cases, 12 peripheral to the scar and 1 within it. Metastases in 31 cases were: pure seminoma (17, 3 with residual testicular seminoma), mixed GCT with seminoma (4, 3 with residual testicular seminoma), mixed nonseminomatous GCT (4, 3 with residual testicular GCT), pure embryonal carcinoma (2), pure teratoma (2, 1 with residual testicular teratoma), and pure yolk sac tumor (2). In 5 cases with clinically diagnosed metastases, there was no histologic documentation of the nature of the metastatic tumor. Testicular tumors in the remaining 6 cases having residual primaries without concomitant metastases were pure seminoma (3), mixed GCT with seminoma (2), and pure embryonal carcinoma (1). The most specific histologic findings of a regressed GCT are a distinct scar in association with either IGCNU or coarse intratubular calcifications; however, many cases lack the latter 2 features. In such cases additional features supportive of regressed GCT include testicular atrophy, microlithiasis and, in the scar, lymphoplasmacytic infiltrates and prominent vascularity. Ghost tubules in many scars are not evidence of a non-neoplastic process but likely reflect regression of tumors with intertubular growth. Intertubular growth is a common finding in seminoma, which is the single most frequent type of regressed GCT, occurring either in pure or mixed form in the metastases of 68% (21/31) of the cases and identifiable in 62% (10/16) of persistent testicular tumors. We conclude that regression of testicular GCTs shows a distinctive constellation of findings that usually permits its recognition. In contrast, nonspecific atrophy lacks distinct scars, and scars from non-neoplastic causes lack most of the associated findings seen in our cases.

Analysis of ovarian teratomas for isochromosome 12p: evidence supporting a dual histogenetic pathway for teratomatous elements

Teratomas are the most common germ cell tumor (GCT) of the ovary and include several types with a range of clinical behavior. As in testicular teratomas, they may be benign, malignant or a component of a mixed GCT. In the testis, data support separate pathogeneses for prepubertal and postpubertal teratomas, with derivation of the former from a nontransformed germ cell and the latter from differentiation of a nonteratomatous, malignant GCT. The absence of cytogenetic abnormalities (including isochromosome 12p (i(12p)) in mature ovarian teratomas suggests that they may be analogous to prepubertal testicular teratomas, but there are no data regarding genetic changes in the teratomatous components of ovarian mixed GCTs. We therefore studied the teratomatous components of six mixed GCTs of the ovary using fluorescence in situ hybridization (FISH) for i(12p). Six mixed GCTs of the ovary occurred in patients 4–33 years of age; all had teratomatous and yolk sac tumor components and three also contained foci of embryonal carcinoma. Using FISH with 12p telomeric and 12 centromeric probes, five of six (83%) cases had detectable i(12p) in their nonteratomatous components, and four of six (66%) in the teratomatous component. One of the two cases without demonstrable i(12p) in the teratomatous portion of the mixed GCT also did not have identifiable 12p abnormalities in other elements of the mixed GCT. By comparison, five pure, mature ovarian teratomas and three pure, immature ovarian teratomas showed no evidence of either i(12p) or other forms of 12p amplification. These findings support that teratoma in mixed ovarian GCTs has a different pathogenesis compared to pure teratoma of the ovary. Furthermore, the findings of i(12p) in both the teratomatous and nonteratomatous components of ovarian mixed GCTs supports that the teratoma derives from other components, similar to the situation in the testis.

Teratoma of the penis in a child

Teratomas are tumors of germ-cell origin, composed of tissues derived from all three germinal layers: ectoderm, endoderm, and mesoderm. Most teratomas have been reported to arise at sites that are midline or paraxial, with the penis being an unusual location for this tumor. The treatment for most pure teratomas is surgical resection. We report a case of primary teratoma of the penis in a 3-month-old child. This is the second reported case of a primary teratoma of the penis and the first in a child.

LATE RELAPSE OF TESTICULAR GERM CELL NEOPLASMS: A DESCRIPTIVE ANALYSIS OF 122 CASES

The problem of late relapse of testicular germ cell tumor (GCT) is poorly understood. No more than approximately 300 cases have been reported to date. It appears that late relapse (L/R) of GCT involves a more aggressive biology than virginal GCT. In the present study we increased the understanding of L/R by analyzing these events in a large patient sample. Late relapse was defined as recurrence of disease more than 2 years after completion of primary treatment. A total of 122 patients (50 with pure seminoma and 72 with nonseminoma) were retrospectively studied. Several parameters were analyzed including age, clinical stage, treatment at primary presentation, occurrence of prior early relapse, interval to L/R, tumor markers, site of relapse, and mode and outcome of L/R treatment. Possible effects of various clinical parameters on treatment results were studied by multivariate statistical analysis. Median age at first presentation was 34 years and 26.5 years in patients with seminoma and nonseminoma, respectively. The intervals to L/R were 42 months (range 25 to 276) in seminoma and 64.5 months (range 28 to 216) in nonseminoma. A total of 75% of nonseminomas but only 20% of seminomas had disseminated disease at first presentation, while 51 patients with nonseminoma had initially received chemotherapy. alpha-Fetoprotein was increased in 45 patients (of 59 eligible) with nonseminoma at L/R, human chorionic gonadotropin in 12 cases. alpha-Fetoprotein levels greater than 100 U/l indicated poor prognosis. Topographically relapses were mainly confined to lymph nodes of the abdomen, chest and neck. Of 72 patients with nonseminoma cure failed in 37 in contrast to only 6 patients with seminoma (of 48 eligible). Inclusion of surgery increased the chance of cure (RR 4.0, 95% confidence interval 0.9-18.5). Late relapses of GCT are biologically and clinically distinct from virginal GCT. These events occur in nonseminoma and seminoma, but clinical features are quite different in the 2 groups. Increase of alpha-fetoprotein is typical in late relapsing nonseminoma and levels of more than 100 U/l appear to indicate poor prognosis. Anatomically L/R presents as lymphadenopathy of abdomen, chest or neck. Treatment should include surgery in nonseminoma. Seminomas and otherwise chemotherapy naive cases might respond to chemotherapy only. Particular risk groups for late relapse are nonseminoma with prior early relapse, patients receiving chemotherapy for disseminated disease at first presentation and those with pure teratoma. These latter subgroups should be followed with annual health examinations for at least 10 years.

Clinical characteristics and outcome of late relapse after cisplatin-based chemotherapy of germ cell tumor. An update

4529 Background: Late relapse of germ cell tumor (GCT) is defined as recurrence after an interval of more than 2 years from initial therapy. Data on clinical characteristics and outcome of patients with late relapses of GCT are sparse. Methods: The charts of 37 patients treated for late relapse after cisplatin-based chemotherapy for GCT from 1983 through 2002 were reviewed (non-seminoma n=36, pure seminoma n=1). Results: Time to late relapse ranged from 25 to 191 months (median 66 months; > 5 years n=21 [57%], > 10 years n=5 [14%]). Tumor marker AFP was elevated in 21 of 36 patients (58%), HCG in 6 cases (17%). The most frequently involved site was the retroperitoneum n=17 (46%) followed by mediastinum n=9 (24%), pelvis, retrocrural space, neck, lung and liver (each site n=4 [11%]). 5 patients (14%) had a late relapse with pure teratoma. 2 patients refused any treatment, 24 patients (65%) underwent chemotherapy as initial treatment for late relapse, 11 patients (30%) surgery. After initial therapy for late relapse 19 patients (51%) achieved no evidence of diesase (NED) status, 9 of whom relapsed again (5 with a second late relapse). After a median follow-up of 52 months (range, 9–168 months) 17 patients (46%) are alive with NED (15 of 27 patients [56%] with disease at one antomic site only), 10 patients (27%) continuously and 7 (19%) after further treatment. 30 patients underwent chemotherapy for management of late relapse or subsequent recurrence, 3 (10%) of whom achieved a durable NED status to chemotherapy alone (1 patient to oral etoposide after failure of high-dose chemotherapy). Conclusions: Resectable disease at one anatomic site is a predictor for favorable outcome of treatment for late relapse. Durable response to chemotherapy alone is rare but occurs even in heavily pretreated patients. As the risk for second late relapse is substantial, lifetime follow-up is necessary. No significant financial relationships to disclose.

Clinical characteristics and outcome of late relapse after cisplatin-based chemotherapy of germ cell tumor. An update

4529 Background: Late relapse of germ cell tumor (GCT) is defined as recurrence after an interval of more than 2 years from initial therapy. Data on clinical characteristics and outcome of patients with late relapses of GCT are sparse. Methods: The charts of 37 patients treated for late relapse after cisplatin-based chemotherapy for GCT from 1983 through 2002 were reviewed (non-seminoma n=36, pure seminoma n=1). Results: Time to late relapse ranged from 25 to 191 months (median 66 months; > 5 years n=21 [57%], > 10 years n=5 [14%]). Tumor marker AFP was elevated in 21 of 36 patients (58%), HCG in 6 cases (17%). The most frequently involved site was the retroperitoneum n=17 (46%) followed by mediastinum n=9 (24%), pelvis, retrocrural space, neck, lung and liver (each site n=4 [11%]). 5 patients (14%) had a late relapse with pure teratoma. 2 patients refused any treatment, 24 patients (65%) underwent chemotherapy as initial treatment for late relapse, 11 patients (30%) surgery. After initial therapy for late relapse 19 patients (51%) achieved no evidence of diesase (NED) status, 9 of whom relapsed again (5 with a second late relapse). After a median follow-up of 52 months (range, 9–168 months) 17 patients (46%) are alive with NED (15 of 27 patients [56%] with disease at one antomic site only), 10 patients (27%) continuously and 7 (19%) after further treatment. 30 patients underwent chemotherapy for management of late relapse or subsequent recurrence, 3 (10%) of whom achieved a durable NED status to chemotherapy alone (1 patient to oral etoposide after failure of high-dose chemotherapy). Conclusions: Resectable disease at one anatomic site is a predictor for favorable outcome of treatment for late relapse. Durable response to chemotherapy alone is rare but occurs even in heavily pretreated patients. As the risk for second late relapse is substantial, lifetime follow-up is necessary. No significant financial relationships to disclose.

Clinical outcome after retroperitoneal lymphadenectomy of patients with pure testicular teratoma

Objectives To determine the pathologic findings and clinical outcome of patients with pure teratoma of the testis who underwent primary or postchemotherapy retroperitoneal lymphadenectomy (RPLND). Methods From January 1989 to February 1998, 29 patients with pure testicular teratoma underwent primary (n = 11) or postchemotherapy (n = 18) RPLND. Results Overall, 23 (79%) of 29 patients had retroperitoneal disease, with 18 (62%) initially presenting with advanced disease. The pathologic stage in the 11 patients undergoing primary RPLND was pN0 in 6 (55%), pN1 in 3 (27%), and pN2 in 2 (18%). Of the 7 patients with clinical Stage I undergoing primary RPLND, 1 had teratoma and 1 had seminoma in the retroperitoneum; of the 4 patients with clinical Stage IIA, 2 had teratoma and 1 had embryonal carcinoma. Four patients were lost to follow-up and the other seven had no evidence of disease (NED) at a median follow-up of 90.4 months, with no relapses. The pathologic findings in the 18 patients undergoing postchemotherapy RPLND revealed fibrosis in 8, teratoma in 9, and yolk sac tumor in 1. At last follow-up, 7 of the 9 patients with teratoma were NED, 1 was dead of disease, and 1 was dead of unknown causes. Of the 8 patients with fibrosis, 6 had NED and 2 were lost to follow-up. The patient with viable cancer had NED at last follow-up. Conclusions These data underscore the metastatic potential of pure testicular teratoma. A significant proportion (45%) of patients with low-stage pure testicular teratoma had retroperitoneal disease. Furthermore, a high proportion (62%) presented initially with advanced disease and demonstrated a considerable risk of relapse despite complete resection or favorable histologic features in the resected retroperitoneal specimen.

Central Nervous System Germ Cell Tumors.

Germ cells tumors most commonly affect children and adolescents, and occasionally arise in the central nervous system. Except for mature teratomas, they are all malignant. Pure germinomas are exquisitely sensitive to treatment and are highly curable with craniospinal radiation therapy. Surgery plays no role other than to establish the histologic diagnosis. Diagnostic confirmation includes normal levels of serum and cerebrospinal fluid alpha-fetoprotein and at most only minor elevations in beta human chorionic gonadotrophin (beta-hCG). Although it has become quite common to use chemotherapy to reduce the dose and field of radiation in the treatment of germinomas, longer follow-up in these patients is revealing a significant number of subarachnoid and ventricular recurrences. A recent follow-up study in patients treated for intracranial germinomas showed no significant difference in the psychosocial functioning of those treated with chemotherapy and radiation compared with those treated with chemotherapy alone, which raises further questions about the rationale for modifying a proven successful treatment. Malignant non-germinomatous germ cell tumors are much more resistant to treatment and difficult to cure. Surgical resection appears to have prognostic significance, although the predilection for midline structures makes complete resection difficult if not impossible at times. The best results have been obtained with platinum-based chemotherapy and full-dose craniospinal radiation therapy. Pure teratomas are not typically responsive to chemotherapy or radiation therapy and surgery is the only proven treatment modality.

Treatment of recurrent malignant sacrococcygeal germ cell tumors: analysis of 22 patients registered in the German protocols MAKEI 83/86, 89, and 96.

To evaluate therapeutic options for recurrent malignant sacrococcygeal germ cell tumors (GCT) following three-agent, cisplatinum-based, first-line chemotherapy and tumor resection. Twenty-two patients were evaluated in 22 first-, 14 second-, five third-, and two fourth-relapse situations. One patient, who relapsed with pure teratoma, was excluded from the analysis of adjuvant treatment. Seventeen patients presented with an isolated local recurrence, two patients showed a distant relapse, and three patients suffered from a combined local and distant recurrence. Twelve patients achieved complete remission (CR) after surgery (n = 12) and adjuvant platinum chemotherapy (n = 10). Seven of these patients remain in continuous CR, and five patients relapsed. All patients who achieved only a partial remission developed a second relapse. Three of 14 patients could be cured after a second (or further) relapse. Altogether, 10 patients survived disease free, and 12 patients died as a result of tumor progression (n = 11) or therapy-related complications (n = 1). The completeness of salvage surgery and clinical remission status after first salvage treatment were the most important prognostic parameters. In addition, patients in first or second relapse with locally advanced or poorly responding tumors benefited from preoperative chemotherapy in combination with regional hyperthermia (RHT). In some patients after microscopically incomplete resection, irradiation at doses > 45 Gy contributed to a favorable outcome. The complete resection of the local recurrence represents the cornerstone of salvage treatment. Preoperative platinum-based chemotherapy, combined with RHT in some patients, facilitates complete tumor resection. Radiotherapy should be reserved for those patients with microscopically incomplete tumor resection. As the chance of cure decreases with further relapses, it is important to establish a stringent therapeutic strategy to avoid significant treatment delays and, most importantly, insufficient local therapy.

Adult primary teratoma of the testis--report on 5 cases in clinical stage I disease.

Testis pure teratoma accounts for 2.7% to 3% of all germ cell tumors in adult where it behaves as a malignant neoplasm. Pure teratoma of the testis presents in clinical stage I disease in 44% of the patients whose risk of having pathological stage II disease is 16.7% to 19.2%. Herein we report on 5 cases of adult pure teratoma of the testis presenting itself in clinical stage I disease. From September 1976 to February 2000, 75 patients underwent orchidectomy for clinical stage I nonseminomatous germ cell cancer of the testis. Testis pure teratoma was detected in 5 patients (7%). Testis tumor markers were evaluated in all cases. Patients underwent imaging examination to detect the clinical stage of the disease. Treatment options after orchidectomy included retroperitoneal lymph node dissection (RPLND) in 4 patients and surveillance in 1. The average age of the patients was 31 years (range 24-45). The tumor was on the left sided in 3 cases (60%) and right in 2 (40%). Tumor average size was 3.2 cm (rang 1-6). Histopathology detected the following subtypes: mature teratoma in 3 cases (60%), immature teratoma in 1 (20%) and teratoma with malignant transformation in (20%). All patients were at clinical stage I disease. Germ cell cancer microscopic metastatic disease including embryonal carcinoma was detected in I dissected lymph node of 1/4 patients (25%). Average follow up was 166 months (range 93-249). All patients were alive and disease free and no relapses were detected during the follow up period. Primary pure teratoma of the testis does not respond to chemotherapy nor does it to radiation therapy. The disease treatment options after orchidectomy for patients with clinical stage I disease include RPLND or surveillance with their relative risks and benefits. RPLND is the chosen treatment because it is both staging and treating. A close a long term follow up is required since pure teratoma metastatic disease may clinically develop after more than 10 years.

Surgical Resection Alone Is Effective Treatment for Ovarian Immature Teratoma in Children and Adolescents: A Report of the Pediatric Oncology Group and the Children’s Cancer Group

This study was conducted to evaluate the routine use of chemotherapy, with its attendant long-term effects, in children and adolescents after the surgical removal of ovarian immature teratoma. Forty-four girls who underwent laparotomy for complete removal of an ovarian tumor containing pure immature teratoma between 1995 and 1996 served as subjects. Patients were classified as having stage I cancer when disease was found in the ovary only with negative peritoneal washings. Among the patients who had adequate staging, no stage II disease was observed. Follow-up for the first 2 years included frequent measurements of serum levels of α-fetoprotein (AFP) and diagnostic imaging studies of the chest and pelvis. Thereafter, patients returned annually for regular physical examinations. At diagnosis, the age range of the subjects was 1.5 to 20 years. Four girls were lost to follow-up, two shortly after surgery and two within 2 years. Nineteen patients were followed for more than 5 years, and four had undergone surgery less than 2 years earlier. Histologic examination found no embryonal carcinoma, choriocarcinoma, or germinoma. Fifteen patients were classified as having grade 1 tumors, 12 had grade 2 tumors, and 2 had grade 3 tumors. On central pathology review, 13 patients were found to have tumors containing microscopic foci of a yolk sac tumor that was previously undetected. Unilateral salpingo-oophorectomy was the treatment selected in 28 patients (64 percent). Only one hysterectomy was necessary. Lymph node samples, obtained from 16 patients, showed mature gliomatosis in three patients. Three subjects had positive peritoneal washings, all of which contained only mature teratomatous or immature glial cells. The 13 patients with ovarian immature teratoma plus yolk sac tumor were slightly older (median, 12 years) than those with pure teratoma (median, 10 years) and were more likely to have larger tumors. Fifty-five percent of the girls with immature teratoma had grade 1 disease, compared with only 8 percent of those whose teratoma contained a yolk sac tumor. Conversely, 46 percent of the children with immature teratoma plus yolk sac tumor were classified as having grade 3 disease, compared with 6 percent of those without yolk sac tumor. Ten of the 13 girls (80 percent) with yolk sac components had measurable levels of AFP, compared with only 10 of 31 of the girls (34 percent) with no yolk sac tumor elements. Furthermore, the median level of AFP was 252 among children with yolk sac tumor, compared with 25 among those without yolk sac tumor. Ovarian immature teratoma containing yolk sac tumor was less likely to rupture during removal than immature teratoma (8 vs. 32 percent). No patients died. There was one malignant recurrence in a 12-year-old girl who had a large ovarian immature teratoma with yolk sac tumor, an initial serum AFP level of 1045 ng/ml, and peritoneal washings and lymph nodes positive for gliomatosis. A sharp rise in her serum AFP level at 18 weeks signaled a recurrence. Two nodules containing grade 2 immature teratoma with yolk sac tumor were found in her liver. She was disease free 57 months after four courses of cisplatin, etoposide, and bleomycin therapy. Two other patients required additional surgical procedures. Both girls underwent exploratory laparotomy for a pelvic mass. One contained ovarian mature cystic teratoma and mature glial implants. The other was composed of multiple mature glial implants on the peritoneal surfaces and on the surface of the remaining ovary, which was removed. Both patients had normal serum AFP levels that did rise, and both continue to be well without additional symptoms. Normal adolescent follicular cysts were frequently observed among the entire study group. Am J Obstet Gynecol 1999;181:353–358

Significance of presence of teratomatous elements in the primary tumour of testicular cancer.

To assess the tumour aggressiveness of teratoma, clinical records of patients with non-seminomatous germ cell testicular cancer were reviewed. Teratomatous elements were found in 57.8% of tumours. The rate of stage I tumours was lower in the teratoma-positive group than in the teratoma-negative group. Lymph node metastasis occurred more frequently than haematogenous metastasis in the teratoma-positive group. Tumour marker response in metastatic stage of teratoma-positive group was very excellent. Even if the radiographic response was not good, most patients were alive without disease after postchemotherapeutic salvage surgery. Furthermore, two patients with pure teratoma, who had tumour recurrence, were successfully treated with the multimodal therapy. Considering the smaller number of stage I patients in the teratoma-positive group than in the teratoma-negative group, the excellent overall response in the teratoma-positive group showed less aggressiveness of the tumour as a whole.

Clinical stage I mature teratoma of the testis--retroperitoneal lymphadenectomy or surveillance?

Pure teratomas are considered to be less aggressive and less likely to metastasize than other nonseminomatous germ cell tumors. Therefore, patients with mature teratomas are considered to be candidates for surveillance protocols. We report on the clinical history and treatment of 44 patients with a primary pure testicular teratoma. In all, 35 patients (79.5%) presented with clinically low-stage disease [n = 26, clinical stage I (59.1%); n = 9, clinical stage IIA/B (20.4%)] and underwent radical orchiectomy followed by retroperitoneal lymphadenectomy (RPLND); nine patients (20.5%) presented with clinically advanced disease (clinical stage IIC to stage IV). Archival tumor blocks were available for pathological reevaluation and serial sections were obtained in all cases. The frequency of lymph node metastases in patients with clinical stage I disease was 19.2%; in patients with clinical stage IIA/B the risk was 66%. Pathohistological diagnosis of mature teratoma was confirmed in all cases; however, 17/20 patients demonstrated scars or calcifications in the adjacent parenchyma, indicating a burned-out tumor and 3/20 demonstrated microfocal germ cell tumor elements. None of the clinical stage I patients relapsed during follow-up; relapse rate among patients with stage IIA/B disease was 33%. Our data demonstrate the malignant potential of pure testicular mature teratoma. Based on our results, metastases in testicular mature teratoma seem to result from metastazising non-germ-cell components undergoing early regression as demonstrated by the high frequency of burnedout tumors. We recommend serial sections of the orchiectomy specimen in all cases of pure mature teratoma for deciding on adequate management: RPLND in cases with associated scars, calcifications or microfocal malignant germ cell components, and surveillance in cases with pure mature teratomas.

The Role of Retroperitoneal Lymphadenectomy in Mature Teratoma of the Testis

Pure testicular teratoma is rare in adulthood with an incidence of 5%. Pure teratoma is considered less aggressive and less likely to metastasize than other nonseminomatous germ cell tumors. Therefore, patients with mature teratoma have been considered candidates for surveillance protocols. We report our experience with 44 cases of primary pure testicular teratoma. We retrospectively identified 44 patients (5.7%) with primary pure teratoma of the testis of the 772 treated for testicular germ cell tumors at our institutions. Archival tumor blocks were available for pathological reevaluation and serial sections were obtained in all cases. A total of 35 patients (79.5%) who presented with clinical low stage disease, including stage I in 26 (59.1%) and stage IIA/B in 9 (20.4%), underwent radical orchiectomy followed by retroperitoneal lymphadenectomy. Nine patients (20.5%) who presented with clinically advanced disease (stages IIC to IV) were treated with primary chemotherapy and secondary retroperitoneal lymphadenectomy of residual masses. The frequency of lymph node metastases was 19.2% in clinical stage I disease and 66% in stage IIA/B. Histopathological diagnosis of mature teratoma was confirmed in all cases. However, of 20 patients 16 (80%) had scars or calcifications in the adjacent parenchyma, indicating a burned out tumor, and 4 (20%) had microfocal embryonal carcinoma. None of the patients with clinical stage I disease had relapse during followup and the relapse rate in those with stage IIA/B disease was 33%. Median followup was 97 months (range 24 to 250). Overall 43% of patients with pure teratoma presented with metastatic disease. Our data demonstrate the malignant potential of pure testicular mature teratoma. Based on our results metastases in testicular mature teratoma seem to result from metastasizing nongerm cell components undergoing early regression, as demonstrated by the high frequency of burned out tumors. We recommend that serial sections be taken of the orchiectomy specimen in all cases of pure mature teratoma to determine adequate management: retroperitoneal lymphadenectomy in cases of associated scars, calcifications or microfocal malignant germ cell components and surveillance in cases of pure mature teratoma.

Primary Pure Teratoma of the Testis

Purpose Despite its histologically benign appearance, primary pure teratoma of the testis is believed to have metastatic potential and behave similarly to other nonseminomatous germ cell tumors. We present our experience with the natural history and management of pure teratoma. Materials and Methods We reviewed the histological findings and clinical history of 15 patients with primary pure teratoma who were treated during a 15-year period, accounting for 4.2 percent of all nonseminomatous germ cell tumors treated during the same period. Fourteen patients were available for followup and are included in this report. Results In 8 patients the tumor was composed entirely of mature teratoma and in 6 immature elements were also present, although this finding was not associated with an increased frequency of metastatic disease. Carcinoma in situ was found adjacent to the tumor in 12 cases. Of 10 patients with stage I disease at presentation who were entered on a surveillance program only 2 have had relapse. The remaining 4 patients had metastatic disease at presentation and, thus, metastatic disease occurred in a total of 6 of the 14 patients (43 percent) with a median followup of 46 months (range 5 to 197). Metastatic disease was confined to the retroperitoneum in all 6 patients and only 2 patients had elevated serum marker levels. Five patients were treated with primary chemotherapy followed by resection of a residual mass and in all cases teratoma was identified in the resected mass. One patient underwent primary surgical excision of a retroperitoneal mass, which contained teratoma and yolk sac tumor, followed by chemotherapy. All patients are alive without evidence of progressive disease. Conclusions In patients with primary pure teratoma of the testis metastatic disease may develop and the metastases may contain other subtypes of nonseminomatous germ cell tumors in addition to teratoma. There is probably a reduced frequency of relapse, which should be considered when advising patients with stage I disease, but otherwise management should be the same as for other testicular nonseminomatous germ cell tumors and the prognosis should be excellent.

Delayed Orchiectomy After Chemotherapy for Metastatic Nonseminomatous Germ Cell Tumors

Purpose We reviewed current experience at our university with delayed orchiectomy after chemotherapy in patients with metastatic nonseminomatous germ cell tumors. Materials and Methods We retrospectively analyzed the records of 160 patients with metastatic germ cell cancer who were given systemic chemotherapy, and subsequently underwent orchiectomy and retroperitoneal lymph node dissection. Results Analysis of 160 testicular specimens revealed necrosis or scar in 70 (43.7 percent), pure teratoma in 50 (31.2 percent) and persistent germ cell cancer in 40 (25 percent). Corresponding incidences of histopathological findings in the post-chemotherapy retroperitoneal lymph node dissection specimens were significantly different, correlating with less than half of the cases (chi-square, p = 0.002). Conclusions Our study confirms the need for delayed orchiectomy after systemic chemotherapy even when there seems to be a partial or complete clinical response at other sites.

Primary Pure Teratoma of the Testis

Primary Pure Teratoma of the Testis

Adult primary pure teratoma of the testis. The Indiana experience

Pure testicular teratoma in adults is a relatively rare malignant tumor with the ability to invade and metastasize. Pure teratoma generally is believed to be less aggressive and less likely to progress, to present in lower stages, and to have better survival rates then other forms of germ cell tumor. Consequently, clinical stage A patients with pure testicular teratoma commonly have been considered to be managed best by surveillance. A computerized database search identified 41 patients presenting to Indian University with pure teratoma in the orchiectomy specimen. These patients were further subdivided into four groups based on clinical stage, as follows: Group I, 18 patients with clinical Stage A disease; Group II, 4 patients with clinical Stages A-B1 disease based on questionable computed tomography findings; Group III, 3 patients with clinical Stage B1 disease; Group IV, 16 patients with advanced stage (B3-C) disease. The experience with these patients was reviewed. The overall risk of lymph node metastasis in retroperitoneal lymph node dissection (RPLND) and the risk of relapse after RPLND for patients with low stage pure testicular teratoma (groups I-III) were 40 and 16%, respectively. In patients with clinical Stage A teratoma, the risk of retroperitoneal metastasis in RPLND was 16.7% and the relapse rate was 11.1%. In addition, nearly 37% of referred patients with pure teratoma presented with advanced disease. These data provide additional confirmation of the metastatic potential of pure testicular teratoma. The proper management of the adult clinical stage A patient with primary pure teratoma of the testis should not necessarily differ from the management of any other histologic type of nonseminomatous testicular tumor. Accordingly, histologic diagnosis of pure teratoma should not mandate surveillance. Instead, patients must be given adequate information regarding management options, as are all other patients presenting with clinical Stage A nonseminoma.

SURGICAL APPROACH TO PATIENTS WITH PROGRESSED-STAGE TESTICULAR CANCER : CLINICAL STUDY OF ONE-STAGE OPERATION FOR RESIDUAL MASSES IN RETROPERITONEAL, THORACIC AND CERVICAL AREAS

Primary chemotherapy and postchemotherapeutic salvage surgery for residual tumors were definite strategies for progressive testicular cancer. To resect multiple metastatic lesions, the one-stage operation consisted of retroperitoneal lymphnode dissection, thoracotomy, sternotomy or cervical dissection was performed by the staffs of urological and surgical units. Although the operation took a rather long time, no definite complications did not occur.The metastatic lesions were able to be resected completely in all cases.Recurrence occured in 2 patients with pure teratoma and another salvage surgery was performed to them. As a current status, three patients have no evidence of disease and one have no radiographical abnormality with a slight elevation of β-hCG level. We concluded that the one-stage operation for multiple lesions was well tolerable and was beneficial for the management of progressive testicular cancer.