Nonteratomatous Germ Cell Tumors Research Articles

Risk Factors for Relapse in Nonseminomatous Testicular Cancer After Postchemotherapy Retroperitoneal Lymph Node Dissection With Viable Residual Cancer.

No consensus exists on the management of men with nonseminoma and viable nonteratomatous germ cell tumor in the postchemotherapy retroperitoneal lymph node dissection (pcRPLND) specimen after first-line chemotherapy. We analyzed surveillance versus different adjuvant chemotherapy regimens and the influence of time to pcRPLND on oncologic outcomes. Data on 117 men treated with cisplatin-based first-line chemotherapy between 1990 and 2018 were collected from 13 institutions. All patients had viable nonteratomatous germ cell tumor in the pcRPLND specimen. Surgery was performed after a median of 57 days, followed by either surveillance (n = 64) or adjuvant chemotherapy (n = 53). Primary end points were progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). After controlling for International Germ Cell Cancer Cooperative Group risk group and percent of viable malignant cells found at RPLND, no difference was observed between men managed with surveillance or adjuvant chemotherapy regarding PFS (hazard ratio [HR], 0.72 [95% CI, 0.32 to 1.6]; P = .4), CSS (HR, 0.69; 95% CI, 0.20 to 2.39; P = .6), and OS (HR, 0.78 [95% CI, 0.25 to 2.44]; P = .7). No statistically significant differences for PFS, CSS, or OS were observed on the basis of chemotherapy regimen or in men treated with pcRPLND ≤57 versus >57 days after first-line chemotherapy. Residual disease with <10% versus ≥10% viable cancer cells were associated with a longer PFS (HR, 3.22 [95% CI, 1.29 to 8]; P = .012). Relapse in the retroperitoneum was observed in 34 (29%) men. Men with a complete resection at pcRPLND and <10% viable cells have favorable outcomes without further treatment. Complete retroperitoneal resection seems more important than early pcRPLND.

Causes and patterns of mortality in patients with lethal germ cell tumor (GCT).

421 Background: Most metastatic GCTs are cured with cisplatin-based chemotherapy. Clinical factors of adverse GCT-specific survival have been identified, however patterns of death are not well-defined and would inform clinical care and biological investigation. Methods: This multi-institutional study pooled data of male pts with death related to GCT from high-volume adult GCT academic centers (Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, Indiana University) over 20 years (1997-2017). Pts were annotated for site, stage, IGCCC risk, histology, primary therapy and relapse variables (including relapse histology, metastatic (met) burden, salvage and palliative therapies), and detailed cause of GCT death. Cox regression assessed associations with survival. Results: The pooled cohort of 620 pts comprised 90% non-seminoma, 21% mediastinal primary and at diagnosis, 59% were stage III, 64% poor risk; 48% received high-dose chemotherapy plus transplantation. Median survival (OS) from first relapse after metastasis was 12.0 mos. Leading causes of death were chemorefractory GCT (83.1%), secondary somatic malignancy (SSM) arising from teratoma (9.4%), acute toxicity (4.5%), late toxicity (2.3%) and progressive untransformed pure teratoma (0.8%). Late relapse (relapse &gt;2 years after 1st-line therapy) occurred in 11.3% at a median of 5.9 yrs. Of these pts, 1/3 were stage I at initial diagnosis and 75% were good or intermediate risk at met diagnosis, and were more likely to have SSM histology/death vs early relapse. Late relapsing disease (HR 0.48, p&lt;0.0001) and presence of SSM (HR 0.74, p=0.017) were associated with longer OS from first relapse after metastasis. Brain metastasis at any time occurred in 29.8%, associated with poorer OS. Conclusions: Comprehensive characterization of GCT-related death reveals a predominant pattern of mortality marked by de novo metastatic, poor-risk disease with subsequent early relapse and death due to chemorefractory non-teratomatous GCT. By contrast, a subset of pts with late-relapsing disease are more likely to have SSM-teratoma and a protracted clinical course. Lethal late relapses frequently occurred beyond 5 years, emphasizing the importance of long-term follow-up.

Outcomes After Multidisciplinary Management of Primary Mediastinal Germ Cell Tumors.

We examined management strategies, overall survival (OS), and progression-free survival (PFS) among patients with PMNSGCTs undergoing resection and multidisciplinary management at a high-volume institution. Outcomes after resection of PMNSGCTs are not well-characterized, with limited data on factors associated with survival. We reviewed patients with PMNSGCT who underwent resection between 1980 and 2019. Median follow-up was 3.4 years. Preoperative therapy (including use of bleomycin), surgical management, recurrence, and survival were examined. Factors associated with survival were analyzed using Cox regression. In total, 113 patients were included [median age, 28 years (range, 16-65)]. Preoperative serum tumor markers (STMs) normalized/decreased in 74% of patients. Pathology included necrosis only (25%), teratoma +/- necrosis (20%), viable nonteratomatous germ cell tumor +/- teratoma (41%), and secondary somatic-type malignancy +/- teratoma (20%). Bleomycin chemotherapy was not associated with pulmonary complications or 90-day mortality. Patients receiving second-line chemotherapy followed by resection had significantly worse OS and PFS than patients receiving first-line chemotherapy followed by resection. On multivariable analysis, R1/R2 resection (HR, 3.92; P < 0.001) and increasing postoperative STMs (HR, 4.98; P < 0.001) were associated with shorter PFS; necrosis on pathology (HR, 0.42, P = 0.043) was associated with longer PFS. In patients with PMNSGCT undergoing resection, completeness of resection, postoperative pathology, and postoperative STMs were associated with PFS. Induction bleomycin was not associated with pulmonary complications or mortality in patients undergoing resection. Patients undergoing second-line chemotherapy followed by resection have a poor prognosis, with long-term survival of 22%.

The utility of CDX2, GATA3, and DOG1 in the diagnosis of testicular neoplasms: an immunohistochemical study of 109 cases

We identified 109 testicular tumors, including pure and mixed germ cell tumors and sex cord-stromal tumors, and conducted immunohistochemical staining for CDX2, DOG1, and GATA3 to address the potential utility of these readily available and commonly used markers in the evaluation of testicular tumors. Their expression has not been previously thoroughly examined in testicular germ cell tumors. The distribution, percentage, and intensity of positivity were assessed. CDX2 was positive in all yolk sac tumors, 25% of choriocarcinomas, 9% of seminomas, and 4% of embryonal carcinomas (sensitivity for yolk sac tumor, 100%; specificity, 89% [teratomas excluded]). CDX2 also stained glandular components within teratomas and identified inconspicuous yolk sac tumor components in 3 cases previously diagnosed as pure embryonal carcinoma. GATA3 was positive in all choriocarcinomas (sensitivity, 100%). Weak GATA3 immunostaining was also seen in 12% of yolk sac tumors and 2 of 2 primitive neuroectodermal tumors. DOG1 was negative in all tumors, but stained spermatocytes and spermatids and the luminal borders of the epididymis and rete testis of nonneoplastic testis. We conclude that CDX2 is a sensitive and relatively specific marker for yolk sac tumor among the nonteratomatous germ cell tumors. It may serve to screen for yolk sac tumor components often overlooked on hematoxylin and eosin-stained slides. GATA3 is helpful in the recognition of trophoblastic cells, especially of intermediate type. DOG1 is a sensitive marker for spermatocytes and needs to be further studied for its significance.

SALL4 Expression in Germ Cell and Non–Germ Cell Tumors

The SALL4 transcription factor is associated with embryonic cell pluripotency and has been shown as a useful immunohistochemical marker for germ cell tumors. However, information of SALL4 distribution in normal human tissues and non-germ cell tumors is limited. In this study we examined normal human tissues and 3215 tumors for SALL4 expression using a monoclonal antibody 6E3 and automated immunohistochemistry. In a 10-week embryo, SALL4 was expressed in ovocytes, intestine, kidney, and some hepatocytes. In adult tissues, it was only detected in germ cells. SALL4 was consistently expressed in all germ cell tumors except some trophoblastic tumors and mature components of teratomas, in which it was selectively expressed in intestinal-like and some squamous epithelia. In non-germ cell carcinomas, SALL4 was detected in 20% of cases or more of serous carcinoma of the ovary, urothelial high-grade carcinoma, and gastric adenocarcinoma (especially the intestinal type). SALL4 was only rarely (≤ 5%) expressed in mammary, colorectal, prostatic, and squamous cell carcinomas. Many SALL4-positive carcinomas showed poorly differentiated patterns, and some showed positivity in most tumor cells mimicking the expression in germ cell tumors. SALL4 was commonly expressed in rhabdoid tumors of the kidney and extrarenal sites and in the Wilms tumor. Expression of SALL4 was rare in other mesenchymal and neuroendocrine tumors but was occasionally detected in melanoma, desmoplastic small round cell tumor, epithelioid sarcoma, and rhabdomyosarcoma. All hematopoietic tumors were negative. SALL4 is an excellent marker of nonteratomatous germ cell tumors, but it is also expressed in other tumors, sometimes extensively. Such expression may reflect stem cell-like differentiation and must be considered when using SALL4 as a marker for germ cell tumors. Observed lack of other pluripotency factors, OCT4 and NANOG, in SALL4-positive non-germ cell tumors can also be diagnostically helpful.

Relationship between primary and metastatic testicular germ cell tumors: a clinicopathologic analysis of 100 cases

Testicular germ cell tumors (GCTs) commonly metastasize to the retroperitoneal lymph nodes (RPLNs). We evaluated 100 cases of RPLN dissection specimens with viable GCTs after chemotherapy and compared them with their corresponding orchiectomy specimens. The mean age of patients was 28 years (range, 15-58 years). The testicular tumors consisted of mixed GCT (n = 72), teratoma (n = 18), seminoma (n = 4), embryonal carcinoma (n = 3), yolk sac tumor (n = 1), and no viable tumor (n = 2). Somatic malignant components were found in 5 cases. The metastatic tumors in the RPLNs consisted of only teratoma (n = 77) and non-teratomatous GCT (n = 23). Twenty-one patients had only teratoma in the RPLNs but not in the testis, and 10 patients had metastatic non-teratomatous GCT components that were not observed in the testis. Six patients had somatic malignant components in the RPLNs, but only one of them had such a component in the testis. Overall, 13 patients died of disease in a mean of 42 months, and the patients with only teratoma in the RPLNs had a lower mortality rate (9%) than those with non-teratomatous components (26%) (P = .044). One patient with somatic components in the primary GCT and 3 patients with somatic components in the metastases died of disease. Our study demonstrates that there is frequent discordance of histologic composition between primary and metastatic testicular GCTs. Teratoma is the most common component in treated GCTs and is usually associated with a more favorable clinical outcome than non-teratomatous GCTs. The presence of somatic components in the RPLNs metastasis indicates a poor prognosis.

A 10-year retrospective review of germ cell tumors not cured with cisplatin-based chemotherapy.

325 Background: In 2011, there were about 8260 cases of Germ Cell Tumor (GCT) diagnosed in the US, of those, 350 or 4% will die of their disease. We sought to review our experience with a 10-year cohort of 819 patients treated for GCT at Dana-Farber and synthesize the cumulative findings of those who died from their disease specifically looking for different sub-types of incurable GCTs. Methods: Retrospective review of 819 germ-cell tumors treated in our center between 2000 and 2010 to identify patients not cured with cisplatin-based chemotherapy. Inclusion criteria were men over the age of 18 treated for malignant germ cell tumor between 2000 and 2010 at the Dana-Farber Cancer Institute that died from their disease. The outcomes of interest were smoking history, extent of disease at diagnosis, primary site of disease, histology, presence of lymphovascular invasion, outcomes to first- and second-line therapies, treatment with high dose chemotherapy (HDC), late relapse, brain metastases, and presence or absence of transformed teratoma as cause of death. Results: 38 men were identified. Median age 35. More than half had a smoking history. 3 presented with clinical stage 1 disease, 8 good-risk metastatic disease, 4 intermediate-risk and 22 poor-risk at diagnosis. The majority (28) had testicular primaries, 7 mediastinal, one pituitary, one retroperitoneal and one unknown. 21 of 48 had complete responses to first-line therapy. 4 received HDC for relapsed disease. 10 relapsed after 2 years of disease-free survival. 7 died of transformed teratoma. 63% progressed directly through cisplatin-based chemotherapy and died as a result of non-teratomatous germ cell tumor burden. 18% died from unresectable or transformed teratoma and 26% died after suffering a late relapse of disease. Conclusions: Within the cohort of patient who died from their GCTs there are three distinct biological subtypes – the majority is platinum-refractory germ cell tumor while unresectable/transformed teratoma and late relapse make up the remainder. Understanding the unique biology of these disease states compared with curable disease may provide informative insights into chemotherapy resistance for cancer in general.

CT findings of primary non-teratomatous germ cell tumors of the mediastinum—A report of 15 cases

To analyze computed tomography (CT) features of primary non-teratomatous germ cell tumors of the mediastinum and to improve the diagnostic efficacy of CT for such tumor. Fifteen patients with primary non-teratomatous germ cell tumors of the mediastinum, proven pathologically, were enrolled. All patients underwent non-enhanced and contrast-enhanced CT examinations. The CT features, including location, size, shape, edge, CT attenuation, involvement of adjacent structure and local or distant metastasis of each lesion were retrospectively analyzed. Each case showed single mass, a total of 15 masses. 11 masses arose within the left anterosuperior mediastinum and 4 masses arose within the right anterosuperior mediastinum. 10 masses appeared lobulated and ill-circumscribed, and 5 masses appeared rounded or oval and well-circumscribed. The maximal diameter of all the masses ranged from 5 cm to 16 cm (mean, 11 cm). 12 masses revealed heterogeneous attenuation on non-enhanced CT images with patchy low-attenuation foci and stippled calcification, and showed moderately heterogeneous enhancement after contrast administration. 3 masses of the patients with seminoma revealed homogeneous attenuation on non-enhanced CT images and showed lightly homogeneous enhancement after contrast administration. Pericardial effusion, pleural effusion and involvement of adjacent vascular structures were observed in 6, 5 and 10 cases, respectively. Pulmonary metastasis were observed in 3 cases. The characteristic CT findings of primary non-teratomatous germ cell tumors of the mediastinum include bulky, ill-circumscribed, lobulated masses, heterogeneous attenuation with low-attenuation foci and calcification on non-enhanced CT images and heterogeneous enhancement after contrast administration. Seminomas may show homogeneous attenuation and homogeneous enhancement after contrast administration. The tumor is apt to involve pericardium, pleura and adjacent vascular structure and develop distant metastasis. Primary non-teratomatous germ cell tumors should be considered when anterosuperior mediastinal masses are detected with these findings, especially in young males.

Reasons for gender differences in prescription of drug therapies in rheumatoid arthritis-results from the database of the German collaborative arthritis centres

We identified 109 testicular tumors, including pure and mixed germ cell tumors and sex cord–stromal tumors, and conducted immunohistochemical staining for CDX2, DOG1, and GATA3 to address the potential utility of these readily available and commonly used markers in the evaluation of testicular tumors. Their expression has not been previously thoroughly examined in testicular germ cell tumors. The distribution, percentage, and intensity of positivity were assessed. CDX2 was positive in all yolk sac tumors, 25% of choriocarcinomas, 9% of seminomas, and 4% of embryonal carcinomas (sensitivity for yolk sac tumor, 100%; specificity, 89% [teratomas excluded]). CDX2 also stained glandular components within teratomas and identified inconspicuous yolk sac tumor components in 3 cases previously diagnosed as pure embryonal carcinoma. GATA3 was positive in all choriocarcinomas (sensitivity, 100%). Weak GATA3 immunostaining was also seen in 12% of yolk sac tumors and 2 of 2 primitive neuroectodermal tumors. DOG1 was negative in all tumors, but stained spermatocytes and spermatids and the luminal borders of the epididymis and rete testis of nonneoplastic testis. We conclude that CDX2 is a sensitive and relatively specific marker for yolk sac tumor among the nonteratomatous germ cell tumors. It may serve to screen for yolk sac tumor components often overlooked on hematoxylin and eosin–stained slides. GATA3 is helpful in the recognition of trophoblastic cells, especially of intermediate type. DOG1 is a sensitive marker for spermatocytes and needs to be further studied for its significance.

Primary Germ Cell Tumors of the Mediastinum: 10 Years of Experience in a Tertiary Teaching Hospital

Germ cell tumors occur mostly in the gonad. Extragonadal germ cell tumors are rare, and most occur in the retroperitoneum and mediastinum. Primary mediastinal germ cell tumors are often found in the anterior portion of the mediastinum and include teratomas and non-teratomatous tumors. Non-teratomatous tumors include seminomas and malignant non-seminomatous germ cell tumors (MNSGCTs). MNSGCTs include yolk sac tumors, choriocarcinomas, embryonal carcinomas, and mixed type germ cell tumors. Teratomas are the most common germ cell tumors of the mediastinum, and seminomas are the most common non-teratomatous germ cell tumors of the mediastinum. Cases of primary mediastinal MNSGCT reported in the literature are rare. In this report, we review all primary mediastinal germ cell tumors from a 10-year period at the Chung-Ho Memorial Hospital of Kaohsiung Medical University. A total of 14 cases were reviewed, including 11 patients with mature teratomas, two with yolk sac tumors, and one with seminoma. We discuss the differences in clinical presentation, histopathologic characteristics, treatment, and prognosis.

Epidermoid Cyst of the Testis

Epidermoid cysts are uncommon testicular tumors accounting for approximately 1% of all testicular neoplasms. The primary differential diagnoses are dermoid cyst and mature teratoma of the testis. Dermoid cyst can be distinguished from epidermoid cyst by the presence of adnexal structures, while teratoma can be distinguished from epidermoid cyst by the presence of other components, commonly from all 3 germ layers, and by its association with intratubular germ cell neoplasia. The distinction from postpubertal mature testicular teratoma is of great importance as teratomas are malignant tumors that may have associated metastasis of either teratomatous or nonteratomatous germ cell tumor types. Treatment of epidermoid cyst of the testis is controversial. Some authors recommend orchiectomy, while others recommend testis-sparing surgery if certain diagnostic criteria are met, including the absence of intratubular germ cell neoplasia in samples of the surrounding parenchyma.

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues

Pediatric brain tumors: statistics of SNUH, Korea (1959-2000).

To investigate the age, gender, location and pathologic diagnosis of brain tumors in pediatric patients (less than 16 years old), we reviewed 677 patients who were operated on at the Department of Neurosurgery, Seoul National University Hospital (SNUH) during the period from January 1959 to June 2000. Only tumors for which pathologic specimens were available were included. Tumors of bone origin, purely extradural mass, nontumorous cystic lesions, and vascular malformations were excluded. The mean age of the 677 patients was 7.8 years and the gender ratio (male-to-female ratio), 1.4:1. Supratentorial tumors (60.0%) were more common than infratentorial tumors (39.1%). Pathological examination showed that the most common tumors were astrocytic tumors (25.7%), medulloblastomas (17.9%), craniopharyngiomas (12.0%), germ cell tumors (11.2%), supratentorial primitive neuroectodermal tumors (ST-PNETs) (5.5%), and neuronal tumors (5.2%). Choroid plexus tumors and ependymal tumors occurred more frequently in early childhood, while pituitary adenomas and non-teratomatous germ cell tumors occurred more frequently in older children. While most tumors were more predominant in males, oligodendroglial tumors and pituitary adenomas were more predominant in females. The relative incidences of germ cell tumors, neuronal tumors, and oligodendroglial tumors increased after the introduction of magnetic resonance imaging (MRI). In contrast, the incidence rates of medulloblastomas and ependymal tumors decreased.

The pathology of late recurrence of testicular germ cell tumors.

A total of 91 men had histologically documented late recurrences of testicular germ cell tumors characterized by a complete response to treatment with a subsequent disease-free interval of at least 2 years and no evidence of a second primary lesion. Ninety percent of the patients for whom information was available received chemotherapy shortly after their initial diagnosis of testicular germ cell tumors; most of the other patients were known to have stage I disease initially. Overall, 60% of patients had teratoma in their late recurrences, including 20 patients (22%) in whom teratoma was the only element. Thus, teratoma was the most common type of neoplasm in late recurrences. Excluding teratoma coexisting with other types of neoplasms, yolk sac tumor was the most frequent type of tumor in patients with late recurrence. It occurred in 47% of patients, either alone or with teratoma, another nonteratomatous germ cell tumor type, or a "nongerm cell malignant tumor." Unusual types of yolk sac tumor, including glandular, parietal, clear cell, and pleomorphic patterns, were seen frequently in late recurrences and often raised differential diagnostic problems with "nongerm cell" carcinomas. A smaller number of late recurrences consisted of other types of neoplasms. Twenty percent of patients with late recurrence had a nonteratomatous germ cell tumor other than yolk sac tumor, either alone, with yolk sac tumor, or with a "nongerm cell malignant tumor." Most of these nonteratomatous germ cell tumors other than yolk sac tumor were embryonal carcinoma, although rarely seminoma and choriocarcinoma were encountered. "Nongerm cell malignant tumors," including both sarcomas and carcinomas of various types, occurred in 23% of late-recurrence patients, either alone or with a nonteratomatous germ cell tumor. Late recurrences were seen in many different sites in these patients, including the retroperitoneum, abdomen, pelvis, liver, mediastinum, lung, bone (femur, vertebra, and rib), lymph nodes outside the retroperitoneum and mediastinum (supraclavicular, neck, and axillary regions), scrotum and inguinal regions, adrenal gland, chest wall, and buttocks. Follow-up data were available for 79 of the 91 patients studied. Duration of follow-up ranged from 2 months to 13 years after the patient's first late recurrences; the mean length of follow-up was 4.8 years. Patients whose late recurrences consisted of teratoma only had the most favorable outcomes, with 79% having no evidence of disease at last follow-up. Patients whose late recurrences consisted of pure "nongerm cell malignant tumor" or pure germ cell tumor (yolk sac tumor or other types) had a much worse prognosis: Only 36% to 37% were alive with no evidence of disease. Patients with two different types of nonteratomatous malignancies in their late recurrences had a dismal clinical course: Only 17% with both yolk sac tumor and other nonteratomatous germ cell tumor had no evidence of disease, whereas no patient with both nonteratomatous germ cell tumor and "nongerm cell malignant tumor" was disease free. Late recurrences consisting of teratoma alone often have a favorable outcome, but the prognosis in all other patients is poor. Furthermore, late recurrence is not likely to respond to chemotherapy and is best treated by surgical excision when possible.

Nonteratomatous germ cell tumors in children

Background/Purpose: Totipotential germ cells may give rise to a broad range of tumors. The teratomatous variety of germ cell tumors has been the subject of several large studies. The goal of the current study was to describe the clinical features of nonteratomatous germ cell tumors (NTGCT) by reviewing a large series of patients. Methods: Between 1945 and 1997, there were 78 cases of nonteratomatous germ cell tumors (NTGCT's) in children at The Children's Hospital, Columbus. Their records were reviewed retrospectively. There were 35 boys and 43 girls (M:F ratio 0.8). Mean follow-up was 87 months. Results : Histological subtypes included germinoma (33 cases, 42%), endodermal sinus tumor (24 cases, 31%), embryonal carcinoma (12 cases, 15%), gonadoblastoma (4 cases, 5%), mixed histology (4 cases, 5%), and choriocarcinoma (1 case, 2%). Forty-two tumors were in gonadal sites, but a significant percentage were extragonadal (36 cases, 46%). Forty-six patients (59%) had localized disease, 18 (23%) had regional disease, and 14 (18%) had metastases. Treatment consisted of surgery and selective chemotherapy and radiation. Complete tumor resection was more likely for gonadal (29 of 42, 69%) than extragonadal primaries (15 of 36, 41%; P ≤ .05). Forty-nine (63%) of all patients survived, whereas 29 (37%) died of their disease. Survival in patients with gonadal primaries (32 of 42, 76%) exceeded that in patients with extragonadal primaries (17 of 36, 47%; P ≤ .01). Survival in patients with localized disease (34 of 46, 74%) exceeded that in patients with regional extention or metastases (15 of 32, 47%; P < .05). Conclusions: This study highlights the fact that tumor location, gonadal versus extragonadal, was important in determining prognosis, whereas tumor histology was not. This may be the result of a higher rate of complete tumor resection for gonadal primaries and underscores the important role of surgery in the optimal treatment of these unusual tumors.

Primary germ cell tumors of the mediastinum

Primary germ cell tumors of the mediastinum are unusual neoplasms with histopathologic features that are similar to those of germ cell tumors in the gonads. However, their clinical features, behavior, and spectrum of pathologic features in the mediastinum have not yet been fully defined. The clinical and pathologic features of 322 cases of primary mediastinal germ cell tumors were reviewed, with special emphasis on teratomatous lesions. The tumors were divided into groups according to their histologic features and correlated with their order of frequency, patient gender and age distribution, and morphologic features. A clinical staging scheme based on the extent and location of the lesions was devised. The overwhelming majority of patients were men (320); only 2 were women (both had teratomatous lesions with additional malignant components). The patients' ages ranged from 1 to 79 years (mean, 40 years). Histologically, all types of germ cell tumors were represented, including 138 teratomas (87 mature teratomas, 6 immature teratomas, and 45 teratomas with additional malignant components); 120 seminomas; 52 nonseminomatous, nonteratomatous germ cell tumors (38 yolk sac tumors, 6 embryonal carcinomas, and 8 choriocarcinomas); and 12 combined germ cell tumors without teratomatous components. The teratomatous lesions with additional malignant components were further separated into subtypes based on the histologic types of their malignant components, i.e., epithelial, mesenchymal, etc. Clinical staging was possible in 242 cases, with 191 cases (79%) in Stage I, 4 cases (1.6%) in Stage II, and 47 cases (19.4%) in Stage III. In each group, the clinical staging correlated well with the clinical outcome for the majority of patients. The results of this study showed that mediastinal germ cell tumors have demographic and histopathologic distributions similar to those of tumors occurring in the male gonads, with teratomatous and seminomatous lesions being the most common. Among the nonseminomatous germ cell tumors in this study, the yolk sac tumors appeared to occur the most frequently (the ratio of yolk sac tumor occurrence to embryonal carcinoma occurrence was 6.1:1). In addition, the subclassification of teratomas with additional malignant components based on the histologic types of malignancies may lead to more therapy choices for patients. At the same time, the use of a clinical staging scheme may be of value in predicting clinical outcome and planning therapy.

Primary germ cell tumors of the mediastinum

BACKGROUND Primary germ cell tumors of the mediastinum are unusual neoplasms with histopathologic features that are similar to those of germ cell tumors in the gonads. However, their clinical features, behavior, and spectrum of pathologic features in the mediastinum have not yet been fully defined. METHODS The clinical and pathologic features of 322 cases of primary mediastinal germ cell tumors were reviewed, with special emphasis on teratomatous lesions. The tumors were divided into groups according to their histologic features and correlated with their order of frequency, patient gender and age distribution, and morphologic features. A clinical staging scheme based on the extent and location of the lesions was devised. RESULTS The overwhelming majority of patients were men (320); only 2 were women (both had teratomatous lesions with additional malignant components). The patients' ages ranged from 1 to 79 years (mean, 40 years). Histologically, all types of germ cell tumors were represented, including 138 teratomas (87 mature teratomas, 6 immature teratomas, and 45 teratomas with additional malignant components); 120 seminomas; 52 nonseminomatous, nonteratomatous germ cell tumors (38 yolk sac tumors, 6 embryonal carcinomas, and 8 choriocarcinomas); and 12 combined germ cell tumors without teratomatous components. The teratomatous lesions with additional malignant components were further separated into subtypes based on the histologic types of their malignant components, i.e., epithelial, mesenchymal, etc. Clinical staging was possible in 242 cases, with 191 cases (79%) in Stage I, 4 cases (1.6%) in Stage II, and 47 cases (19.4%) in Stage III. In each group, the clinical staging correlated well with the clinical outcome for the majority of patients. CONCLUSIONS The results of this study showed that mediastinal germ cell tumors have demographic and histopathologic distributions similar to those of tumors occurring in the male gonads, with teratomatous and seminomatous lesions being the most common. Among the nonseminomatous germ cell tumors in this study, the yolk sac tumors appeared to occur the most frequently (the ratio of yolk sac tumor occurrence to embryonal carcinoma occurrence was 6.1:1). In addition, the subclassification of teratomas with additional malignant components based on the histologic types of malignancies may lead to more therapy choices for patients. At the same time, the use of a clinical staging scheme may be of value in predicting clinical outcome and planning therapy. Cancer 1997; 80:681-90. © 1997 American Cancer Society.

Outcome analysis for patients with persistent nonteratomatous germ cell tumor in postchemotherapy retroperitoneal lymph node dissections.

We review the long-term outcome of patients with viable nonteratomatous germ cell tumor (NTGCT) in retroperitoneal lymph node dissection (RPLND) specimens after primary or salvage chemotherapy, and the impact of postoperative therapy with two courses of standard-dose cisplatin-based induction chemotherapy. All patients with viable NTGCT in postchemotherapy RPLND specimens from surgeries performed at Indiana University between July 1975 and March 1991 were retrospectively reviewed. Of 580 postchemotherapy RPLNDs performed, 133 had viable NTGCT in their pathology specimens. Of these 580 postchemotherapy RPLNDs, 417 were performed after primary chemotherapy, and 43 (10%) had viable NTGCT in their pathology specimens. There were 163 RPLNDs performed after salvage chemotherapy and 90 (55%) had viable NTGCT in their pathology specimens. After primary chemotherapy, 34 of 43 had complete resections, and 27 of the 34 received postoperative cisplatin-based chemotherapy. Nineteen of 27 (70%) are continuously disease-free (c-NED). All seven who received no postoperative chemotherapy have relapsed. After salvage chemotherapy, 53 of 90 had complete resections. Of those 53, 25 received postoperative chemotherapy, and nine (36%) are c-NED. Twenty-eight received no postoperative chemotherapy, and 12 (43%) are c-NED. Overall, 43 of 133 patients had incomplete resections, and only four are currently disease-free. There were four postoperative deaths (PODs). (1) Incomplete resection of viable NTGCT after primary or salvage chemotherapy portends a very poor prognosis. (2) For patients with complete resection of viable NTGCT following primary chemotherapy, two additional courses of cisplatin-based chemotherapy appear to be safe and effective therapy for reducing the risk of relapse. (3) Additional standard-dose chemotherapy appears to offer no benefit to patients with viable NTGCT in the resected specimen after salvage chemotherapy.

The significance of atypia within teratomatous metastases after chemotherapy for malignant germ cell tumors.

The completely resected teratomatous metastases of 55 patients who had been treated with cisplatin-based combination chemotherapy for non-seminomatous germ cell tumors were reviewed to see if cellular atypia had an effect with respect to recurrent disease. The degree of atypia of the epithelial and mesenchymal elements was assessed on the basis of the cytologic features and mitotic activity. Twenty-three percent of the cases contained high-grade epithelial elements, whereas high-grade mesenchymal elements occurred in 18% of the cases; in addition there were nine cases classified as showing frankly malignant teratomatous elements. The presence of cytologically disturbing epithelial and mesenchymal elements (which, however, lacked an invasive malignant pattern) correlated with an increased incidence of recurrent teratoma compared to less atypical teratomatous elements (23% vs. 6% for epithelial elements, and 18% vs. 9% for mesenchymal elements, respectively). This difference, however, was not statistically significant (P greater than 0.05). There was no correlation between teratomatous atypia and recurrent, non-teratomatous germ cell tumor. The presence of an invasive malignant pattern did identify patients at significantly increased risk for recurrent teratoma-derived tumor. The authors conclude that cytologic atypia in the absence of invasion is not sufficient justification for altering the usual therapeutic strategies for patients with teratomatous metastases.