Diagnosis Of Germ Cell Tumors Research Articles

Cytologic features of extragonadal germ cell tumors

The objective of the current study was to evaluate and describe the cytologic features of extragonadal germ cell tumors (GCTs), both primary and metastasis from gonadal sites, in fine-needle aspiration cytology. Aspirates from 88 extragonadal GCTs were retrieved with their clinical features and cytologic smears. The smears were assessed for cellularity, cell patterns, and cytologic features, which were summarized. Histopathology was available in 47 cases, and cytohistologic correlation was done in all such cases. Of 88 cases, 57 with adequate cytologic material were analyzed. Each type of GCT, except for embryonal carcinoma, had characteristic morphologic features. Seminomas had dyscohesive tumor cells with well defined, vacuolated cytoplasm; prominent nucleolus; and background lymphocytes. 'Tigroid' background was noted in only a minority of cases. Yolk sac tumors revealed papillary fragments of tumor cells with metachromatic basement membrane-like material in the fragments. Mixed germ cell tumors were difficult to diagnose except for cases in which more than 1 type of GCT was observed on cytologic smears. In 37% of cases with mixed GCT, only 1 component was observed on cytology. Fine-needle aspiration cytology can reliably offer a diagnosis of GCT at extragonadal sites, even in rare locations and in patients in whom metastatic tumor may be the first clinical presentation. Immature teratoma and mixed GCTs pose a significant problem in cytology because of sampling error on needle aspiration. At extragonadal sites, the list of differential diagnoses is wider than that for gonadal GCTs.

Method Validation for Cerebral Spinal Fluid Human Chorionic Gonadotropin Measurement with the Advia Centaur®2

Intracranial germ cell tumors account for 0.4%–3.4% of all brain tumors (1). These tumors can be divided into 2 groups, germinomas and nongerminomatous germ cell tumors. Germinomas, which are fairly treatable, arise from primordial germ cells that fail to migrate correctly in embryogenesis. Nongerminomatous germ cell tumors (including choriocarcinomas), which are more refractory to treatment, are differentiated tumors. Measurement of human chorionic gonadotropin (hCG)1 is an important adjunct method in the diagnosis of germ cell tumors. At high concentrations hCG can be detected in serum, but measurement of hCG concentrations in cerebral spinal fluid (CSF) is a more sensitive and reliable indicator of tumor presence (1). Pure germinomas are associated with very low concentrations of hCG in both serum and CSF. A subset of nongerminomatous germ cell tumors contains syncytiotrophoblastic giant cells. These tumors are associated with moderately increased concentrations of hCG (<1000 IU/L) in the serum, CSF, or both, and the survival rate in patients suffering these tumors is poorer than that for patients with pure germinomas …

Changes in sexual functioning after germ cell tumor (GCT) therapy estimated by patients and their partners

5086 Background: Only few studies have addressed sexual difficulties and sexual satisfactions as an area of subjective quality- of-life in long-term survivors of GCT. We investigated the sexual functioning and sexual well-being in patients (pts) and their partners after GCT therapy. Methods: 474 pts treated for GCT between 1979 and 2000 were asked to complete a self-report questionnaire on psychosocial dimensions such as sexual functioning and partnership. Female partners were asked to complete a part of the questionnaire. Results: A completed questionnaire was returned by 341 of 474 pts (71.9%) and by 196 female partners of the responding pts (57.5%). The median age of the pts was 41.9 years at the time of the study and 31.2 years at the time of GCT diagnosis (median follow-up 9.6 yrs). Of 327 pts who provided information on their marital status 203 (62%) were married/lived in a partnership, 101 (31%) were single and 24 (7%) divorced. 81 pts (25%) complained of decreased sexual attractivity which was more frequently reported in pts divorced (42%) than in singles (30%) or married pts (19%). Libido loss, arousal loss, decreased erection, decreased ejaculation and decreased orgasm intensity were reported by 66 (19%), 73 (21%), 70 (21%), 110 (32%) and 70 (21%) pts, respectively. All of these complaints more frequently occurred in pts ≥40 yrs at time of the study compared to age <40 (p<0.001). Of responding couples more males than females reported to be sexually unsatisfied (32% vs 23%) after GCT therapy. Sexual satisfaction decreased with the duration of the partnership in females (p=0.005) but not in males (p=0.5). More pts than female partners reported fear of sexually dissatisfying the partner before (10% vs 4%) and after GCT therapy (24% vs 7%). More females (22%) than pts (14%) reported a positive influence of the disease on their partnership with a significant difference observed in partnerships of <1 year duration (67% vs 32%, p=0.007). Conclusions: About 20% of pts are limited in sexual functioning after GCT therapy. Overall, more female partners than pts have a favorable perception of the influence of the disease on the partnership. No significant financial relationships to disclose.

Pelvic teratoma with extensive spinal involvement in a neonate: an important differential diagnosis

A 6-week-old girl presented with an abdominal mass and spinal cord compression. Clinical and radiological features indicated a diagnosis of congenital neuroblastoma. Histology revealed a diagnosis of germ cell tumour after therapy for neuroblastoma had been commenced. This is, to the authors' knowledge, the first reported case of paediatric dumbbell retroperitoneal teratoma.

Clinical utility of OCT4 in diagnosis of germ cell tumor

原始生殖细胞具有多向分化的潜能,由其发生的肿瘤形态变化多样,种类较多,如精原细胞瘤、无性细胞瘤、生殖细胞瘤和胚胎性癌,然而这些生殖细胞来源的肿瘤容易与一些非生殖细胞来源的肿瘤相混淆。

The Volatility Effect

<h3>BACKGROUND AND PURPOSE:</h3> Suprasellar papillary craniopharyngiomas and germ cell tumors in adults share some clinical and imaging similarities but have different therapeutic strategies and outcomes. This study aimed to evaluate the pretreatment diagnosis of these 2 tumors to improve the therapeutic outcome. <h3>MATERIALS AND METHODS:</h3> We retrospectively enrolled 18 adults with papillary craniopharyngiomas and 17 with germ cell tumors. The MR imaging findings were evaluated, including signal change and anatomic extension. The medical records were reviewed to collect clinical findings, management, and outcomes. <h3>RESULTS:</h3> The clinical findings of papillary craniopharyngiomas versus germ cell tumors were as follows: age: 46 ± 13.9 years versus 23 ± 7.1 years (<i>P</i> &lt; .0001); diabetes insipidus: 2/18 (11%) versus 11/17 (65%) (<i>P</i> = .001); recurrence 13/16 (81%) versus 4/17 (24%) (<i>P</i> = .0031). The MR imaging findings of papillary craniopharyngiomas versus germ cell tumors were as follows—pituitary stalk thickening: 1.6 ± 0.4 mm versus 5.4 ± 4.2 mm (<i>P</i> &lt; .0001); vertical infundibular extension: 1/18 (6%) versus 16/17 (94%) (<i>P</i> &lt; .0001); sagittal spheric shape: 17/18 (94%) versus 1/17 (6%) (<i>P</i> &lt; .0001); diffusion restriction: 1/17 (6%) versus 8/12 (67%) (<i>P</i> = .0009). <h3>CONCLUSIONS:</h3> Younger age, diabetes insipidus, MR imaging characteristics of restricted diffusion, and vertical infundibular extension favor the diagnosis of germ cell tumors. Spheric shape without infundibular infiltration provides clues to papillary craniopharyngiomas, which originate from the pars tuberalis and are located outside the third ventricle. We suggest that suprasellar germ cell tumor is possibly an intraventricular lesion. Appropriate treatment planning can be initiated according to the diagnosis and anatomic location.

Improvement in the outcome of children with germ cell tumors

To describe the clinical characteristics and estimate the survival of children and adolescents with germ cell tumors treated with cisplatin-based combination chemotherapy according to three different protocols in Brazil. From 1983 to 1997, 106 patients were treated at the Hospital do Cancer, Sao Paulo for a diagnosis of germ cell tumor. We performed a retrospective review of the clinical and histopathological data to identify prognostic factors and evaluate their outcome. Patients were treated with only surgery (n = 32), surgery and radiotherapy (n = 1) and chemotherapy (n = 73). From 1983 to 1986 (period I), there were 30 patients and 21 received chemotherapy according to the modified VAB-6 protocol. Twenty-two of 35 patients registered between 1987 and 1991 (period II) were treated with EPO/VAC combination chemotherapy. From 1991 to 1997 (period III), there were 41 patients and 31 received chemotherapy according to the Brazilian TCG-91 protocol. Important prognostic factors included stage (P < 0.001), metastatic status (P < 0.001) and surgical procedure at diagnosis (P < 0.001). An incremental improvement in outcomes was noted across the periods of treatment (P = 0.070). Five-year OS was respectively 42.9 +/- 10.8%, 53.9 +/- 11.4% and 80.6 +/- 7.1% for periods I, II, and III for the patients who received chemotherapy. An improvement in the survival of children with germ cell tumors was achieved in the most recent trial (TCG-91) with a risk adapted approach incorporating only cisplatin and etoposide. These results indicate that in selected patients complex three-agent regimens may not be necessary to achieve long term survival.

Embryonic Stem Cell Transcription Factor Signatures in the Diagnosis of Primary and Metastatic Germ Cell Tumors

The core embryonic stem cell transcription factors (TFs) OCT3/4 (OCT4), NANOG, and SOX2 have shared as well as nonoverlapping roles in stem cell growth and differentiation. These same TFs are also expressed in various types of human germ cell tumors (GCTs), implicating them in regulation of tumor growth and differentiation. Although NANOG and OCT3/4 are sensitive and specific markers for seminoma and embryonal carcinoma, neither factor aids in the clinically important distinction of seminomatous from nonseminomatous tumors. In contrast, expression profiling data suggest that SOX2 may help with this distinction. To determine if a panel of embryonic stem cell TFs (NANOG, OCT3/4, and SOX2) can facilitate the identification and distinction of seminomatous from nonseminomatous GCTs, we evaluated their expression by immunohistochemistry in primary testicular (n=41) and metastatic retroperitoneal (n=43) GCTs. Our results confirm NANOG and OCT3/4 as sensitive and specific markers for primary seminoma and embryonal carcinoma and demonstrate the novel finding that NANOG is a marker for metastatic GCTs. In addition, SOX2 is expressed in embryonal carcinoma but not pure seminoma and is therefore a useful diagnostic marker for distinguishing seminomatous and nonseminomatous GCTs. In summary, we find that the embryonic stem cell TF signature of seminoma is NANOG+, OCT3/4+, and SOX2-, whereas embryonal carcinoma is NANOG+, OCT3/4+, and SOX2+, and expect these immunohistochemical profiles will facilitate the diagnosis of both primary and metastatic GCTs.

Smoking cessation in long-term survivors of germ cell tumour

Long-term survivors of germ cell tumours (GCT) are at increased risk of cardiovascular morbidity. We investigated the use of tobacco in patients after therapy for GCT. Four hundred and seventy-four patients treated between 1979 and 2000 at the University of Munich were asked to complete a self-report questionnaire on psychosocial dimensions which included items on tobacco smoking before and after treatment of GCT. Three hundred and forty-one patients (72%) returned a completed questionnaire. The median follow-up period was 9.6 years. 160 of 341 patients (47%) reported to smoke at the time of GCT diagnosis. Of those, 134 (84%) had changed their smoking behavior with 32 patients (20%) having reduced, 56 (35%) having intermittently quitted and 46 (29%) having definitively quitted smoking. Patients reduced or stopped smoking irrespective of tumour histology, tumour stage, whether they had received chemotherapy or not, and irrespective of the number of chemotherapy courses applied. Most patients changed their habit of tobacco smoking after diagnosis and treatment of GCT but only a minority of patients are sustained quitters. Patients with GCT should be strongly encouraged to stop smoking or to participate in smoking cessation programs.

Intra‐abdominal mass aspirate from an alopecic dog

An 11-year-old female Yorkshire terrier was presented to the University of Minnesota Veterinary Medical Center for evaluation of a palpable intra-abdominal mass and alopecia. Abdominal ultrasonography revealed a large, complex, cavitary mass in the left caudal region of the abdomen. A fine needle aspirate of the mass was collected. A population of markedly pleomorphic, large, round to polygonal cells were found singly and in small noncohesive aggregates. The cells contained scant, clear to blue-gray cytoplasm, large, round to oval nuclei, and distinctly stippled to reticular chromatin. Cytologic findings were consistent with a tumor of ovarian origin, with a primary differential diagnosis of germ cell tumor. Hormonal analysis of serum revealed a marked increase in 14-OH-progesterone concentration (2.71 ng/mL, reference interval 0.05-0.69 ng/mL). Ovariohysterectomy was performed, and the mass was found to be in the area of the left ovary. Histologic evaluation of the reproductive tract confirmed a diagnosis of left ovarian dysgerminoma. Based on immunohistochemical stains, the tumor was negative for c-kit (CD117c) and single cells were positive for neuron-specific enolase. A right ovarian cyst and squamous metaplasia of the right uterine horn also were diagnosed. The cyst was presumed to be the source of 14-OH-progesterone, which likely resulted in the squamous metaplasia and dermatopathy. Three months after surgery, the progesterone concentration had returned to normal and the alopecia had nearly resolved. Dysgerminomas in dogs are reported rarely, but have a distinctive, recognizable, cytologic appearance and should be included in the differential diagnosis of an intra-abdominal mass in a reproductively intact female dog.

Smoking cessation in long-term survivors of germ cell tumor (GCT)

4737 Background: Cigarette smoking is the most significant source of preventable morbidity and premature mortality in developed countries. As long-term survivors of GCT have been found to be at an increased risk of developing vascular events and second cancer, smoking cessation could be an important factor to improve health status and overall survival. The purpose of this study was to investigate the use of tobacco in patients after GCT therapy. Methods: 474 patients treated for GCT between 1979 and 2000 at the University of Munich were asked to complete a self-report questionnaire on psychosocial dimensions which included items on tobacco smoking before and after treatment of GCT. These data were compared with those on smoking habits in the general male population in Germany. Results: 341 of 474 patients (71.9%) returned a completed questionnaire. The median age of responding patients was 41.9 years at the time of the study and 31.2 years at the time of GCT diagnosis. The median follow-up period was 9.6 years. 114 of 341 patients (33.4%) reported to smoke at the time of the study. 108 were cigarette smokers with 67.7% smoking more than 10 cigarettes a day. With respect to different groups of age (< 20 years, 20 - 29 years, 30 - 39 years and 40 - 49 years), 33.3%, 37.7%, 36.1% and 18.2% reported to smoke. The corresponding percentages of smoking patients in the general male population are 27.9%, 43.3%, 45.5%, and 42.7%. After diagnosis and/or therapy of GCT 83.8% of smoking patients had changed their smoking behavior by either having reduced (20%), having temporarily stopped (28.1%) or having definitively stopped smoking (35.7%). Patients reduced or stopped smoking irrespective of tumor histology (seminoma vs nonseminoma; p=0.33), tumor stage (I vs. II vs III; p=0.47), whether they had received chemotherapy or not (p=0.89), and irrespective of the number of chemotherapy courses applied (p=0.88). With advancing age more patients tended to stop smoking. Conclusions: After diagnosis and treatment of GCT most patients changed their habit of tobacco smoking. This resulted in lower numbers of smoking patients as compared to the general male population in Germany. No significant financial relationships to disclose.

A practical approach to the reporting of germ cell tumours of the testis

Germ cell tumours (GCT) present many different challenges for diagnostic histopathologists and a new classification by the World Health Organization has recently introduced some new entities. The accurate diagnosis of GCT is essential for appropriate treatment. Therapy is also influenced by staging and, therefore, careful macroscopic examination is vital. Many prognostic markers have been used, many of which are still contentious. Close co-operation with both the surgical and medical teams is vital for consistent treatment and the avoidance of misunderstandings. A number of entities may mimic GCT, leading to misdiagnosis. The morphological appearances of GCT are particularly difficult to interpret if chemotherapy has already been administered. Many transformations of GCT may be seen including sarcomatous, carcinomatous and neuroendocrine malignancies. These require different treatment regimens and may arise many years after the primary excision.

Metastatic Seminoma with Cervical Lymphadenopathy as the Initial Manifestation

Advanced testicular germ cell tumors commonly involve cervical lymph nodes. In most circumstances, the diagnosis of germ cell tumor is established before the neck disease is noted. In rare cases, these tumors have been found along with cervical lymphadenopathy in patients with a previously undiagnosed primary tumor. In this article, we report the unusual case of a 71-year-old man whose metastatic seminoma initially manifested as an asymptomatic neck mass. This finding reinforces the need to include metastatic disease in the differential diagnosis of neck masses. Our discussion of this case focuses on the appropriate management of cervical metastases of germ cell tumors.

Multicenter study of human immunodeficiency virus-related germ cell tumors.

Testicular germ cell tumors (GCT) occur at increased frequency in men with human immunodeficiency virus (HIV). This multicenter study addresses the characteristics of these tumors. Patients with HIV-related GCT were identified from six HIV treatment centers. The incidence was calculated from the center with the most complete linked oncology and HIV databases. Thirty-five patients with HIV-related GCT were identified. The median age at GCT diagnosis was 34 years (range, 27 to 64 years). The median CD4 cell count was 315/mm3 (range, 90 to 960/mm3) at this time. The histologic classification was seminoma in 26 patients (74%) and nonseminomatous GCT in nine patients (26%). Twenty-one patients (60%) had stage I disease and 14 patients had metastatic disease. Overall six patients relapsed, three died from GCT, and seven died from HIV disease, resulting in a 2-year overall survival rate of 81%. HIV-related seminoma occurred more frequently than in the age- and sex-matched HIV-negative population, with a relative risk of 5.4 (95% confidence interval, 3.35 to 8.10); however, nonseminomatous GCT did not occur more frequently, and there was no change in the incidence of GCT since the introduction of highly active antiretroviral therapy. Testicular seminoma occurs significantly more frequently in HIV-positive men than in the matched control population. Patients with HIV-related GCTs present and should be treated in a similar manner to those in the HIV-negative population. After a median follow-up of 4.6 years, 9% of the patients died from GCT. Most of the mortality relates to HIV infection.

Detection and diagnostic utilization of placental alkaline phosphatase in muscular tissue and tumors with myogenic differentiation.

Placental alkaline phosphatase (PLAP) is normally produced by primordial germ cells and syncytiotrophoblasts, and the detection of its expression has been useful in the diagnosis of germ cell tumors. We have recently observed PLAP immunoreactivity in normal human adult and fetal muscle tissue. Based on this observation, we explored the possible role of PLAP in the diagnosis of soft tissue tumors. A total of 271 tumors were studied. These included tumors with myogenic, neural, fibrous, myofibroblastic, lipomatous, neuroepithelial, perivascular, and epithelial differentiation. A formalin-fixed, paraffin-embedded section from each tumor was stained with PLAP monoclonal antibody using standard immunohistochemical methods preceded by antigen retrieval. In addition, western blotting with PLAP monoclonal antibodies was performed on fresh samples from a uterine leiomyoma, grossly normal myometrium, and placenta. Also, formalin-fixed sections of fetal skeletal muscle were labeled with double immunohistochemistry techniques using antibodies to myogenin and PLAP. Cytoplasmic PLAP reactivity was detected in all leiomyomas and rhabdomyosarcomas (100%), 7 of 15 (46%) leiomyosarcomas, 15 of 19 (79%) desmoplastic small round cell tumors, 2 of 15 (13%) gastrointestinal stromal tumors, 1 of 8 (13%) Wilms' tumors, 1 of 9 synovial sarcomas (9%), and 2 of 7 (29%) myofibroblastic tumors. No PLAP reactivity was detected in hyperplastic scars, nodular fasciitis, or the other remaining soft tissue and epithelial tumors. Double immunohistochemistry studies showed coexpression of myogenin and PLAP in fetal skeletal muscle cells, and western blot analysis showed a 70-kDa band in samples derived from grossly normal placenta, benign myometrium, and a uterine leiomyoma. PLAP immunoreactivity is detected in soft tissue tumors with known myogenic differentiation. PLAP immunoreactivity seems to relate to the degree of myogenic differentiation in soft tissue tumors and is more frequently expressed in cells with skeletal muscle differentiation and least in those with myofibroblastic features. The biologic function of PLAP in muscle and tumors with myogenic differentiation is unknown and merits further investigation. In addition to its role as a germ cell marker, PLAP may also be used as a myogenic marker in the diagnosis of soft tissue tumors.

Fine-needle aspiration biopsy of nonteratomatous germ cell tumors of the mediastinum.

We assessed the usefulness of fine-needle aspiration biopsy (FNAB) in the diagnosis of mediastinal germ cell tumors (GCTs). In the archives of 3 pathology departments, we found records of 7 patients with mediastinal GCTs who underwent mediastinal FNAB as part of the diagnostic workup. The FNAB smears, results of the immunocytochemical analysis, the corresponding histologic findings, and the clinical charts were reviewed. All patients were men (age range, 24-44 years; mean, 32 years). One patient had a history of testicular mixed GCT 10 years earlier. The 6 primary mediastinal GCTs consisted of 3 seminomas and 3 yolk sac tumors. Based on the cytologic features and immunocytochemicalfindings, a cytologic diagnosis of GCT was made in 5 cases, including the case of metastatic GCT In 2 cases, the differential diagnosis was between poorly differentiated carcinoma and GCT Results of ancillary studies were noncontributory in 1 case, and the aspirate of the second case demonstrated extensive necrosis. Our findings demonstrate that a diagnosis of mediastinal GCT, primary or secondary, can be established with a high degree of accuracy on the basis of FNAB. Immunocytochemical analysis helps confirm the diagnosis.

MRI of intracranial germ-cell tumours

Our aim was to review the MRI appearances of primary intracranial germ-cell tumours (GCT). We reviewed the MRI studies of 32 patients: 19 with germinomas, five with teratomas, one with an embryonal carcinoma, five with mixed and two with malignant nongerminomatous GCT. Eleven were in the pineal region, 12 suprasellar, five in the both sites, two in the basal ganglia and two in the corpus callosum. Contrast-enhanced images were available for 27 patients. The solid parts of GCT were nearly isointense with grey matter on both T1- and T2-weighted images. In seven patients with nongerminomatous GCT high-signal components were found on T1-weighted images, representing haemorrhage, high-protein fluid or fat. Cystic components were detected in 17 of 27 patients; eight germinomas and all nine nongerminomatous GCT had cysts. The solid components of germinomas enhanced homogeneously in eight cases and heterogeneously in 10, while all nongerminomatous GCT showed heterogeneous enhancement. MRI features tumours can facilitate correct diagnosis of GCT, including histological subtypes.

Germ cell tumors in patients infected by the human immunodeficiency virus.

The objective of this study was to assess the natural history of the two disease courses, patient immune system tolerance, and results of therapy in human immunodeficiency virus (HIV)-infected patients with germ cell tumors (GCT). From 1985 to 1996, 34 HIV-infected men received a diagnosis of GCT. Their charts were analyzed retrospectively. Sixteen patients had seminomas, and 18 had nonseminomatous GCTs (NSGCT); 71% had International Union Against Cancer (UICC), 1997 Stage I-II GCTs. At the time of chemotherapy, 69%, 6%, and 25% of patients with advanced NSGCT were in the International Germ Cell Consensus Classification (IGCCC) good, intermediate, and poor prognostic group, respectively. All except 1 of the 10 patients with advanced seminomas were in the IGCCC good prognostic group. At diagnosis of GCT, 85% of patients were classified as having asymptomatic HIV infection or only persistent generalized lymphadenectomy. The median CD4 cell count was 325/microL (range, 6-1125). Overall, 26 patients were given chemotherapy, but the planned dose intensity was respected in only 15 (57%) patients. Severe toxic effects included febrile neutropenia in 35% of patients. During chemotherapy, zidovudine, prophylactic granulocyte colony-stimulating factor (G-CSF), and a Pneumocystis carinii prophylaxis were given in 19%, 23%, and 35% of cases, respectively. CD4 cell count decreased in 7 (64%) of 11 patients during chemotherapy. Infradiaphragmatic radiotherapy was given in 10 cases and was clinically well tolerated. At a median follow-up of 27 months (range, 3-150), 50% of patients were alive, and only 18% of patients died of GCT. Two patients developed a non-GCT malignancy while in complete remission, namely, Hodgkin disease and an acute leukemia. The prognosis of GCT in HIV-infected patients is mostly dictated by the HIV infection. Patients should be treated according to stage and histologic subtype, although dose reduction of chemotherapy might be necessary in approximately half of the patients. Close surveillance of neutrophil and CD4 cells counts, as well as the use of G-CSF and systematic anti-Pneumocystis carinii prophylaxis are recommended during chemotherapy. The use of highly active antiretroviral therapy during chemotherapy for GCT requires a prospective assessment.

The relative risk of second nongerminal malignancies in patients with extragonadal germ cell tumors

BACKGROUND Apart from a recognized association between extragonadal mediastinal germ cell tumors (GCT) and the occurrence of hematologic malignancies, the risk of developing second nongerminal solid tumors after the diagnosis or treatment of extragonadal GCT is unknown. METHODS Six hundred thirty-five consecutive patients with extragonadal GCT treated at 11 centers in the U.S. and Europe during the era of cisplatin-based chemotherapy (1975–1996) were included into a large database. These patients were evaluated for the occurrence of second malignancies. RESULTS No treatment-related leukemia was observed in 611 patients treated with chemotherapy. In 7 patients, second solid tumors were observed, resulting in a frequency of 1.86% (95% confidence interval [95% CI], 1.79–1.93%) after a median follow-up of 55 months (95% CI, 50–60 months) (annual incidence, 0.30% [95% CI, 0.14–0.59]). Four solid tumors (57%) developed in patients with primary mediastinal and 3 tumors (43%) developed in patients with retroperitoneal GCT. Three patients (43%) had a nonseminomatous and 4 patients (57%) had a seminomatous histology. Six patients had been treated with chemotherapy and one patient with radiotherapy. Six of 7 solid tumors (86%) had developed within 5 years and 7 of 7 solid tumors within 10 years of diagnosis. The median time period to the occurrence of neoplasia was 47 months (range, 9–145 months). Four cutaneous tumors were observed (melanoma, two patients; basal cell carcinoma, one patient; and squamous cell carcinoma, one patient); the other three tumors were angiosarcoma, nonsmall cell lung carcinoma, and colorectal carcinoma. The overall risk for developing a second tumor was not increased compared with an age-matched general population with a standard incidence ratio (SIR) of 1.49 (95% CI, 0.60–3.06). An elevated risk for skin tumors was observed in all extragonadal GCT patients (SIR, 4.00 [95% CI, 1.09–10.24]), as well as in the subgroup of patients treated with chemotherapy (SIR, 5.33 [95% CI, 1.45–13.65]). CONCLUSIONS This analysis excludes an increased biologic risk of developing second solid malignancies in patients with extragonadal GCT except for the previously reported association between primary mediastinal nonseminoma and hematologic disorders. The overall risk of developing second malignancies in extragonadal GCT patients appears to be comparable to that in patients with primary testicular carcinoma. The incremental occurrence of skin malignancies in patients treated with chemotherapy should be investigated further. Cancer 2000;88:2629–35. © 2000 American Cancer Society.

The relative risk of second nongerminal malignancies in patients with extragonadal germ cell tumors

Apart from a recognized association between extragonadal mediastinal germ cell tumors (GCT) and the occurrence of hematologic malignancies, the risk of developing second nongerminal solid tumors after the diagnosis or treatment of extragonadal GCT is unknown. Six hundred thirty-five consecutive patients with extragonadal GCT treated at 11 centers in the U.S. and Europe during the era of cisplatin-based chemotherapy (1975-1996) were included into a large database. These patients were evaluated for the occurrence of second malignancies. No treatment-related leukemia was observed in 611 patients treated with chemotherapy. In 7 patients, second solid tumors were observed, resulting in a frequency of 1.86% (95% confidence interval [95% CI], 1.79-1.93%) after a median follow-up of 55 months (95% CI, 50-60 months) (annual incidence, 0.30% [95% CI, 0.14-0.59]). Four solid tumors (57%) developed in patients with primary mediastinal and 3 tumors (43%) developed in patients with retroperitoneal GCT. Three patients (43%) had a nonseminomatous and 4 patients (57%) had a seminomatous histology. Six patients had been treated with chemotherapy and one patient with radiotherapy. Six of 7 solid tumors (86%) had developed within 5 years and 7 of 7 solid tumors within 10 years of diagnosis. The median time period to the occurrence of neoplasia was 47 months (range, 9-145 months). Four cutaneous tumors were observed (melanoma, two patients; basal cell carcinoma, one patient; and squamous cell carcinoma, one patient); the other three tumors were angiosarcoma, nonsmall cell lung carcinoma, and colorectal carcinoma. The overall risk for developing a second tumor was not increased compared with an age-matched general population with a standard incidence ratio (SIR) of 1.49 (95% CI, 0.60-3.06). An elevated risk for skin tumors was observed in all extragonadal GCT patients (SIR, 4.00 [95% CI, 1. 09-10.24]), as well as in the subgroup of patients treated with chemotherapy (SIR, 5.33 [95% CI, 1.45-13.65]). This analysis excludes an increased biologic risk of developing second solid malignancies in patients with extragonadal GCT except for the previously reported association between primary mediastinal nonseminoma and hematologic disorders. The overall risk of developing second malignancies in extragonadal GCT patients appears to be comparable to that in patients with primary testicular carcinoma. The incremental occurrence of skin malignancies in patients treated with chemotherapy should be investigated further.