A germ cell tumor occurs due to dysregulated growth and differentiation of germ cells.
Presentation
Symptoms associated with germ cell tumors vary substantially from individual to individual. The most commonly reported signs and symptoms include abdominal pain, shortness of breath, wheezing, irregularity in the shape of the abdomen, irregular testicular size, swelling or mass that may be felt or seen, incontinence, leg weakness in case the malignant mass is in the sacrum, constipation and sometimes elevated beta-human chorionic gonadotropin and alpha-fetoprotein (AFP). In some cases, diagnosis can be difficult to establish because of similar presentations of many other medical conditions.
Entire Body System
- Pain
An unusual case of chest pain in a young male patient is presented that is caused by an anterior mediastinal mass associated with pericarditis and right ventricular outflow obstruction. [ncbi.nlm.nih.gov]
Through our renowned program, patients experience unparalleled family support, a nationally recognized pain management team, and compassionate, coordinated care. [childrensmn.org]
Symptoms may include a heavy feeling in the pelvis pain in the lower abdomen bleeding from the vagina weight gain or loss abnormal periods unexplained back pain that gets worse gas, nausea, vomiting, or loss of appetite to diagnose ovarian cancer, doctors [icd9data.com]
Germ Cell Tumor Symptoms - a solid testicular mass, with or without associated testicular pain - a solid ovarian mass discovered on ultrasound done for abdominal pain - a mass visible in the lower back, near the anus, often in an infant - respiratory [hopkinsmedicine.org]
- Swelling
A 12-year-old boy presented with progressively enlarging scalp swelling and features of raised intracranial pressure. The lesion was totally excised and calvarial defect reconstructed using titanium mesh. [ncbi.nlm.nih.gov]
Within the testes, the tumor is a visible, painless, firm swelling or may lead to precocious puberty. In the ovary it is not as visible and the tumor may grow very large before being noticed. This can lead to abdominal pain, abdominal swelling. [cincinnatichildrens.org]
[L. tumor, a swelling] tumor (too'mor) [L. tumor, a swelling] 1. A swelling or enlargement; one of the four classic signs of inflammation. 2. An abnormal mass. [medical-dictionary.thefreedictionary.com]
It is also more common in men who have had abnormal testicle development have had an undescended testicle have a family history of the cancer symptoms include pain, swelling or lumps in your testicles or groin area. [icd9data.com]
The most common symptoms of GCT include swelling, mass that can be touched or seen, increased levels of alpha-fetoprotein (AFP), high level beta-human chorionic gonadotropin (ß-HCG), constipation, incontinence, leg weakness, abdominal pain or shortness [creative-biolabs.com]
- Weakness
The most common symptoms in children with mediastinal GCTs, which are nonspecific, are dyspnea, chest pain, cough, hemoptysis, vena cava occlusion syndrome, and fatigue/weakness. [ncbi.nlm.nih.gov]
The most common symptoms of GCT include swelling, mass that can be touched or seen, increased levels of alpha-fetoprotein (AFP), high level beta-human chorionic gonadotropin (ß-HCG), constipation, incontinence, leg weakness, abdominal pain or shortness [creative-biolabs.com]
Symptoms can include: A mass or swelling Constipation Incontinence Abnormally shaped or sized testicle Leg weakness Elevated levels of alpha-fetoprotein (a protein in the blood) Elevated levels of beta-human chorionic gonadotropin (a hormone that can [mottchildren.org]
[…] or holding in your pee, if the tumor is near your pelvis) Breast growth, pubic hair, or vaginal bleeding at an earlier age than normal Belly or chest pain Lump or a mass in the belly, back, or testicles Testicles that aren’t the right shape or size Weakness [webmd.com]
- Fatigue
The most common symptoms in children with mediastinal GCTs, which are nonspecific, are dyspnea, chest pain, cough, hemoptysis, vena cava occlusion syndrome, and fatigue/weakness. [ncbi.nlm.nih.gov]
GCTs that occur in the brain interfere with the flow of fluid around the brain and spinal cord with symptoms of: • Headaches; • Nausea; • Vomiting; • Memory loss; • Fatigue; • Gait disturbances; • Uncontrolled eye movements; and • Double vision. [secure.ssa.gov]
As the disease progresses, symptoms may include shortness of breath, persistent cough/wheezing, hoarseness, bone pain, fatigue and loss of appetite and weight. [health.am]
Fatigue and weakness are other common side effects of chemotherapy. [encyclopedia.com]
While not everyone with these tumors has symptoms, the following symptoms may be associated with extragonadal germ cell tumors: Chest pain Breathing problems Cough Fever Headache Change in bowel habits Fatigue Difficulty walking Trouble with vision How [brighamandwomens.org]
- Inflammation
One of the four signs of inflammation (t., calor, dolor, rubor) enunciated by Celsus. [medical-dictionary.thefreedictionary.com]
This may indicate malignancy, although infection or inflammation may also appear brighter on a PET scan. Biopsy, the removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer. [brighamandwomens.org]
Microalbuminuria, decreased fibrinolysis, and inflammation as early signs of atherosclerosis in long-term survivors of disseminated testicular cancer. [mijn.bsl.nl]
Laboratory of Immune Systemic Interactome in Cancer & Kidney (ISICK) http://Biomed.snu.ac.kr/research/snuisick Cancer metastasis, Cancer stem cells, Immune-Cancer cross-talk, Immune regulation, Tissue-resident immune cells, Tissue-Immune cross-talk, Kidney inflammation [biomed.snu.ac.kr]
Germinoma Mimicking Brain Inflammation: A Case Report. Child Neurol Open. 2019;6: 2329048X19848181. 35. Mesquita Filho P, Santos F, Köhler L, Manfroi G, De Carli F, Augusto de Araujo M et al. [revistas.javeriana.edu.co]
Respiratoric
- Cough
A 28-year-old Japanese male presented with cough and left-sided chest pain for 6 weeks. The patient had a mediastinal tumor with metastases to the right lung, lymph nodes, and bones at initial presentation. [ncbi.nlm.nih.gov]
As the disease progresses, symptoms may include shortness of breath, persistent cough/wheezing, hoarseness, bone pain, fatigue and loss of appetite and weight. [health.am]
[…] adjacent structures, hemorrhage or necrosis Choriocarcinoma Epidemiology Usually men in 20s with elevated hCG and gynecomastia, impotence Prognostic factors Poor prognosis Case reports 13 year old boy with shortness of breath, chest pain, fever, irritable cough [pathologyoutlines.com]
- Hoarseness
As the disease progresses, symptoms may include shortness of breath, persistent cough/wheezing, hoarseness, bone pain, fatigue and loss of appetite and weight. [health.am]
The condition may also lead to: Difficulty in breathing, swallowing Cough Weight loss Facial swelling Hoarseness of voice When Extra Gonadal Germ Cell Tumors occur in the retroperitoneum it may cause: Abdominal pain (the pain is usually a pelvic pain) [dovemed.com]
Additional symptoms include exertional dyspnea, cough, dysphagia, and hoarseness. Superior vena caval syndrome develops in approximately 10% of patients. Systemic symptoms related to metastatic lesions are uncommon. [ncbi.nlm.nih.gov]
Gastrointestinal
- Abdominal Pain
CASE: A 16-year-old female patient presented with abdominal pain and an 11-cm adnexal mass on ultrasound. An emergent laparoscopic salpingo-oophorectomy was performed without complication. [ncbi.nlm.nih.gov]
The most common symptoms of GCT include swelling, mass that can be touched or seen, increased levels of alpha-fetoprotein (AFP), high level beta-human chorionic gonadotropin (ß-HCG), constipation, incontinence, leg weakness, abdominal pain or shortness [creative-biolabs.com]
The most prominent symptoms are abdominal pain, shortness of breath, wheezing, irregular testicular size and the appearance of a mass along the midline of the body. Workup includes blood tests, imaging studies, and biopsy. [symptoma.com]
A 28-year-old male with complaints of abdominal pain and lumbago, without any abnormality in both testes by physical and ultrasonographic examination, showed retroperitoneal tumor by abdominal computed tomography. [academic.oup.com]
Ovarian and abdominal tumors often present with symptoms like abdominal pain or constipation. As a tumor gets bigger, it may become evident as an abdominal mass. [curesearch.org]
- Vomiting
Have vomited. They should remain home for 24 hours after vomiting stops. Have diarrhea. They should remain home for 24 hours after diarrhea stops. [redclayschools.com]
Symptoms may include a heavy feeling in the pelvis pain in the lower abdomen bleeding from the vagina weight gain or loss abnormal periods unexplained back pain that gets worse gas, nausea, vomiting, or loss of appetite to diagnose ovarian cancer, doctors [icd9data.com]
Nausea and vomiting are also fairly common side effects of many chemotherapy drugs. Radiation to the brain or the GI tract can also cause nause and vomiting. [encyclopedia.com]
Nausea and vomiting Some of the chemotherapy drugs used may make your child feel sick or vomit. We will give anti-sickness drugs at the same time to stop nausea and vomiting. These are usually very effective. Hair loss Temporary hair loss is common. [royalmarsden.nhs.uk]
Symptoms may include headache, nausea, vomiting, memory loss, lethargy, difficulty walking, inability to look upward, uncontrolled eye movements or double vision. [ucsfbenioffchildrens.org]
- Nausea
Mid chest GCT may cause: • Chest pain; • Breathing problems; • Cough; • Weight loss; • Nausea; and • Fevers. Lower back GCTs may present as a mass in the lower abdomen or buttocks. [secure.ssa.gov]
Drugs that combat nausea and vomiting can be prescribed, but are often not effective for anticipatory nausea. There are self-help measures that can be tried. [encyclopedia.com]
Symptoms may include a heavy feeling in the pelvis pain in the lower abdomen bleeding from the vagina weight gain or loss abnormal periods unexplained back pain that gets worse gas, nausea, vomiting, or loss of appetite to diagnose ovarian cancer, doctors [icd9data.com]
Abdominal pain (the pain is usually a pelvic pain) Abdominal swelling due to the mass or due to fluid accumulation in the belly (called ascites) Increased abdominal girth due fluid accumulation (ascites) Persistent feeling of abdominal bloating with nausea [dovemed.com]
Symptoms may include headache, nausea, vomiting, memory loss, lethargy, difficulty walking, inability to look upward, uncontrolled eye movements or double vision. [ucsfbenioffchildrens.org]
- Diarrhea
Have diarrhea. They should remain home for 24 hours after diarrhea stops. Have a persistent cough It is great that students want to come to school, but it is very important to stop the spread of germs throughout the school. [redclayschools.com]
Cardiovascular
- Chest Pain
An unusual case of chest pain in a young male patient is presented that is caused by an anterior mediastinal mass associated with pericarditis and right ventricular outflow obstruction. [ncbi.nlm.nih.gov]
pain, fever, irritable cough and weight loss ( Zhongguo Dang Dai Er Ke Za Zhi 2009;11:517 ) 14 year old boy with placental site trophoblastic tumor ( Hum Pathol 2005;36:581 ) 25 year old man with choriocarcinoma masquerading as relapsed Hodgkin lymphoma [pathologyoutlines.com]
Psychiatrical
- Hunger
The food in Jannah never rotting and so delicious it will make any person on earth live without feeling hunger forever. [flickr.com]
Urogenital
- Cryptorchidism
While a high clinical suspicion may avoid unnecessary orchiectomy in young patients, its association with disorders such as cryptorchidism should make us suspect the possible presence of a concomitant germ cell neoplasia. [ncbi.nlm.nih.gov]
Predisposing factors: cryptorchidism, testicular dysgenesis (e.g. testicular feminization and Klinefelter syndrome), prior or family history of GCT. Caucasian > African Americans. [auanet.org]
It is important to note that the development of cancer with cryptorchidism does not always occur. [symptoma.com]
Specifically, males with cryptorchidism (failure of the testes to descend into the scrotal sac) have an increased risk to develop testicular germ cell tumors. Cryptorchidism can occur alone; however, and is also present in some genetic syndromes. [childrensnational.org]
- Urinary Retention
Internal tumors may cause constipation, urinary retention and pain. More Information [curesearch.org]
The most common symptoms of germ cell tumors include: A swelling or mass that your child’s doctor can feel or see Abdominal pain Constipation, urinary retention, incontinence and leg weakness caused by a tumor in the sacrum (bottom of the spinal column [rileychildrens.org]
- Testicular Disease
Female Urogenital Neoplasms Endocrine System Diseases Gonadal Disorders Genital Neoplasms, Male Genital Diseases, Male Testicular Diseases Mesonephroma Trophoblastic Neoplasms Adenocarcinoma Pregnancy Complications, Neoplastic Pregnancy Complications [clinicaltrials.gov]
Neurologic
- Headache
A 26-year-old Caucasian sailor, with no past medical history aside from headache for the last 1 week, was found dead in his cabin. The body was stored in a refrigerator on board and disembarked for autopsy 3 days later. [ncbi.nlm.nih.gov]
Symptoms may include headache, nausea, vomiting, memory loss, lethargy, difficulty walking, inability to look upward, uncontrolled eye movements or double vision. [ucsfbenioffchildrens.org]
GCTs that occur in the brain interfere with the flow of fluid around the brain and spinal cord with symptoms of: • Headaches; • Nausea; • Vomiting; • Memory loss; • Fatigue; • Gait disturbances; • Uncontrolled eye movements; and • Double vision. [secure.ssa.gov]
- Irritability
“By irritating the skin by having something constantly against it for hours on end and pushing the wax deeper in the canal, you’re constantly irritating the ear.” [philadelphia.cbslocal.com]
needs restraint Day 60 Irritable, needs restraint IVIG Day 67 Less confused, less irritable 19 (99) 55.9 60 Day 82 Discharge, K-MMSE 28 CSF WBC and RBC counts are expressed in cells per cubic millimeter. [jkna.org]
[…] of adjacent structures, hemorrhage or necrosis Choriocarcinoma Epidemiology Usually men in 20s with elevated hCG and gynecomastia, impotence Prognostic factors Poor prognosis Case reports 13 year old boy with shortness of breath, chest pain, fever, irritable [pathologyoutlines.com]
Context, Collocation imeti, zdraviti plju�nico; umreti za plju�nico English translation pneumonia Definition Respiratory disease characterized by inflammation of the lung parenchyma (excluding the bronchi) with congestion caused by viruses or bacteria or irritants [lojze.lugos.si]
Workup
Workup of germ cell tumors necessarily involves many tests. It includes blood tests such as a complete blood count (CBC), chemistry, liver function tests (LFTs), kidney function tests (creatinine and blood urea nitrogen), tumor cell markers and genetic studies. Imaging studies are critical. CT scan, MRI, ultrasound and bone scans can all be used to assess the tumor and potential metastasis. A testicular ultrasound is performed when a diagnosis of malignant germ cell cancer is established to rule out cancer in the gonads.
Subtypes of germ cell tumors have particular characteristic features that differentiate them. Seminomas rarely invade adjacent structures and tend to metastasize to the bone and the lymph nodes. Calcifications can be detected within the tumor but they are uncommon. On histopathological analysis, the tumor appears bulky, lobulated, homogeneous and tends to present as an anterior mediastinal mass. On the other hand, nonseminomatous mediastinal germ cell tumors can metastasize to adjacent organs, the lymph nodes and to distant sites. They generally appear as irregular masses in the anterior mediastinum. Characteristic findings include areas of low attenuation resulting from necrosis, presence of cysts and hemorrhage. In contrast, mature teratomas exhibit calcifications in around 25% of samples. Uncommonly, a bone or a tooth are detected. Other characteristic features include a well defined, anterior mediastinal mass with irregular walls of various thickness, cyst formation with heterogeneous composition and the presence of fluid, calcium, and fat attenuation.
Treatment
Treatment varies depending on several factors such as the extent of the tumor, the age of the patient, medical history, future expectations and tolerance to certain treatment options. A number of treatment modalities are available. These include surgery, radiation, chemotherapy, hormonal replacement when required, bone marrow transplantation, antibiotics to treat existing infections or to prevent their occurrence, supportive care to manage the severe side effects of the treatment and follow-up care to rule out recurrence, assess response to the treatment and control late complications.
Malignant germ cell tumors follow a staging procedure similar to epithelial ovarian cancers. For women who still desire a child, the unilateral salpingo-oophorectomy is recommended. This operation preserves the uterus, fallopian tube and ovary on the non-diseased site. On the other hand, women who do not desire more pregnancies can undergo a bilateral salpingo-oophorectomy with hysterectomy. In general, it is not possible to conserve both ovaries in case the disease is bilateral.
The majority of germ cell tumors require a chemotherapy regimen based on three main agents. The regimen is termed BEP or PEB and consists of bleomycin, etoposide, and cisplatin.
Prognosis
The prognosis of germ cell tumors can be assessed with the International Germ Cell Consensus Classification [9]. The classification tool enables the physician to predict the risk of relapse for patients diagnosed with germ cell tumors, subsequent to treatment. On the other hand, computerized tomography (CT), magnetic resonance imaging (MRI) and ultrasound (US) aid in visualizing the tumor and can thus establish a risk for malignant transformation. This is especially helpful as links have been established between cystic and benign tumors, and malignant and solid tumors [10]. These imaging studies can further allow the selection of the best surgical plan. It is worth mentioning that choriocarcinoma of the testicles is considered the germ cell tumor with the worst prognosis.
The prognosis of germ cell tumors is affected by access to treatment. Early diagnosis improves 5-year survival, according to a 1993 study involving 454 men diagnosed between 1975-1989 with nonseminomatous germ cell tumors. Furthermore, treatment in cancer units improves survival by up to 60%, even for patients diagnosed with malignancies with the worst prognosis.
Etiology
The causative mechanisms responsible for germ cell tumors remain unknown. Nonetheless, some inherited and non-inherited defects have been shown to significantly increase the risk. For example, cryptorchidism, defined as the failure of the descent of the testes to the scrotum, results in an increased risk of testicular germ cell cancer. The age at which the testicle is surgically ascended (orchidopexy) plays a critical role. Patients who had the operation before 13 years have a relative risk of 2.23 of developing testicular germ cell cancer. In contrast, those who underwent orchidopexy at 13 years or later have a relative risk of 5.4 [2]. It is important to note that the development of cancer with cryptorchidism does not always occur. On the other hand, an additional or a missing sex chromosome may lead to defects in the reproductive system, and subsequent development of germ cell tumors.
Scientists suggest that extragonadal germ cell tumors result from a defect during embryogenesis. This eventually leads to misplacement of primordial germ cells, and ultimately to local transformation and tumor growth. Extragonadal germ cell tumors tend to occur in the midline of the body. In particular, in the anterior abdominal wall, liver, stomach, prostate, vagina, the thyroid, the submandibular area, the suprasellar area, the palate and in the orbit.
On the other hand, risk factors for nonseminomatous testicular tumors are various. These include gonadal dysgenesis, exposure to chemical carcinogens, orchitis, trauma, prenatal exposure to high levels of estradiol and a history of testicular cancer. One study, conducted on 44,684 Swedish men and published in 2005 after 25 years of follow-up, reported a link between testicular cancer and elevated cholesterol levels [2]. However, future studies need to expand on and confirm these findings in other populations.
Epidemiology
Extragonadal germ cell tumors make up 5 to 10% of all germ cell tumors in the United States. In Norway, the incidence of extragonadal germ cell tumors has been reported to be 0.5 for every 100,000 individuals, representing 2% of testicular cancers [3]. On the other hand, intracranial germ cell tumors are rare in the West and make up 0.3 to 3.4% of all intracranial tumors. However, they represent 2.1 to 12.7% of all cases of intracranial tumors in Japan [4]. Studies by Rusner et al performed on 16,000 patients diagnosed with malignant extragonadal germ cell tumors between 1998 and 2008 concluded that different etiologies are associated with differences in age-specific and age-standardized incidence [5].
On the other hand, nonseminomatous testicular tumors have a peak incidence between 20 and 34 years of age. They tend to occur more frequently among whites than African Americans. They remain, however, relatively infrequent, despite the fact that they are the most commonly encountered solid malignancy among young and healthy individuals. The incidence of nonseminomatous testicular tumors in the United States is 5.44 for every 100,000 individuals [6]. There have been some recent alarming signals. Studies report an increase in the incidence of 46% in the United States between 1975-2001, even after the introduction of platinum-based chemotherapy [6]. Other reports suggest that incidence has substantially increased among military personnel between 1988 and 1996 [7].
Pathophysiology
Several genetic mutations are involved in malignant transformation. In particular, an increase in the 12p gene, due to a duplication of the chromosomal arm or of the gene itself, has been strongly linked to germ cell tumors. This mutation is present in both advanced disease and carcinoma in situ. Other important features include an overexpression of the CCND2 gene. CCND2 is normally present on the 12p13 band and results in the activation of cdk4/6. CDk4/6 helps move the cell from G1 to S in the cell cycle.
On the other hand, intracranial germ cell tumors are characterized by the imbalance of p53 and mdm2 levels. Normally, mdm2 inhibits p53, induces apoptosis and regulates the G1 to S checkpoint. Mdm2 is under the control of ARF, which in turn results from the expression of the p14ARF gene. ARF binds mdm2 and degrades it [8]. In intracranial germ cell tumors, a mutation in ARF leads to an increase in mdm2 levels and a subsequent impairment of p53.
Nonseminomatous germ cell tumors can be classified into four subtypes: teratomas, choriocarcinomas, embryonal carcinomas and yolk sac tumors. Mixed tumors represent a mixture of all of these histological types. Some tumors possess both seminomatous and nonseminomatous components. They are generally considered nonseminomatous because the latter determines prognosis and response to treatment.
Prevention
There are no current preventive measures for germ cell tumors.
Summary
Germ cells are the cells that constitute the reproductive organs in both males and females. Germ cell tumors can be either benign or malignant. They tend to occur in the reproductive organs and in the midline of the body and are classified into germinomas or seminomas and nonseminomatous germ cell tumors [1]. The latter usually grow faster, are less responsive to chemotherapy and radiotherapy and have a poor prognosis.
Germ cell tumors are rare tumors. The incidence of nonseminomas is approximately 5.44 for every 100,000 individuals. The latter tend to affect healthy and young individuals between the ages of 20 and 34 years. The underlying causative mechanisms remain unknown, although several risk factors have been identified. For example, cryptorchidism, or the failure of the descent of the testes into the scrotum, increases the risk of testicular germ cell cancer. Other risk factors include genetic or inherited conditions that affect sex chromosomes and that can lead to abnormalities in the reproductive organs. The pathophysiologic mechanisms underlying germ cell tumors involve genetic mutations of critical cell regulatory agents. A mutation in the 12p gene due to a chromosomal arm duplication is strongly associated with germ cell tumors. Other molecules that play an important role are mdm2, cdk4/6, and p53.
Patients with germ cell tumors present with a range of symptoms depending on the site and location of the tumor. The most prominent symptoms are abdominal pain, shortness of breath, wheezing, irregular testicular size and the appearance of a mass along the midline of the body. Workup includes blood tests, imaging studies, and biopsy. Treatment varies according to the patient and the subtype of the tumor. It encompasses chemotherapy, radiotherapy, surgery, bone marrow transplantation and hormonal replacement. A typical chemotherapy regimen for germ cell tumors consists of bleomycin, etoposide, and cisplatin.
Patient Information
Germ cells are the cells that develop during the formation of the embryo and later become part of the reproductive organs. Abnormal tumors from these cells occur when there is dysregulated growth and differentiation. These tumors can occur in the reproductive organs or outside. This is because many germ cell tumors remain in other parts of the body during the development of the embryo. Germ cell tumors can be benign or malignant and are classified histologically into many types. One type called seminoma or germinoma has significantly better prognosis than nonseminomatous tumors.
Patients can present with a multitude of symptoms, making the diagnosis sometimes particularly challenging. The most common symptoms are abdominal pain, the presence of a mass in the body, irregular testicular size, shortness of breath and wheezing. The physician must perform a very broad workup to establish diagnosis and guide treatment. The workup will include blood tests, imaging with x-ray, computerized tomography or magnetic resonance imaging, biopsy and histological analysis.
Treatment of germ cell tumors can vary considerably based on the specific circumstances of the patient and the type of tumor involved. Chemotherapy, radiotherapy, surgery, bone marrow transplantation and hormonal replacement are all potential treatment modalities.
References
- Ulbright TM. Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues. Mod Pathol. 2005;18 Suppl 2:S61-79.
- Pettersson A, Richiardi L, Nordenskjold A, et al. Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med. 2007;356(18):1835-41.
- Dueland S, Stenwig AE, Heilo A, et al. Treatment and outcome of patients with extragonadal germ cell tumours--the Norwegian Radium Hospital's experience 1979-94. Br J Cancer. 1998;77(2):329-35.
- Takeda S, Miyoshi S, Ohta M, et al. Primary germ cell tumors in the mediastinum: a 50-year experience at a single Japanese institution. Cancer. 2003;97(2):367-76.
- Rusner C, Trabert B, Katalinic A, Kieschke J, Emrich K, Stang A. Incidence patterns and trends of malignant gonadal and extragonadal germ cell tumors in Germany, 1998-2008. Cancer Epidemiol. 2013;37(4):370-3.
- Sokoloff MH, Joyce GF, Wise M. Testis cancer. J Urol. 2007;177(6):2030-41.
- Thompson IM, Optenberg S, Byers R, et al. Increased incidence of testicular cancer in active duty members of the Department of Defense. Urology. 1999;53(4):806-7.
- Iwato M, Tachibana O, Tohma Y, et al. Alterations of the INK4a/ARF locus in human intracranial germ cell tumors. Cancer Res. 2000;60(8):2113-5.
- [No authors listed]. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol. 1997;15(2):594-603.
- Stankovic ZB, Djukic MK, Savic D, et al. Pre-operative differentiation of pediatric ovarian tumors: morphological scoring system and tumor markers. J Pediatr Endocrinol Metab. 2006;19(10):1231-8.